{"id":34475,"date":"2022-05-18T20:00:29","date_gmt":"2022-05-18T12:00:29","guid":{"rendered":"https:\/\/swarma.org\/?p=34475"},"modified":"2022-05-18T20:00:29","modified_gmt":"2022-05-18T12:00:29","slug":"%e5%89%8d%e6%b2%bf%e7%bb%bc%e8%bf%b0%ef%bc%9a%e6%8f%8f%e8%bf%b0%e7%94%9f%e7%89%a9%e7%b3%bb%e7%bb%9f%e6%b6%8c%e7%8e%b0%e8%a1%8c%e4%b8%ba%e7%9a%84%e6%99%af%e8%a7%82%e5%92%8c%e6%b5%81%e7%90%86%e8%ae%ba","status":"publish","type":"post","link":"https:\/\/swarma.org\/?p=34475","title":{"rendered":"\u524d\u6cbf\u7efc\u8ff0\uff1a\u63cf\u8ff0\u751f\u7269\u7cfb\u7edf\u6d8c\u73b0\u884c\u4e3a\u7684\u666f\u89c2\u548c\u6d41\u7406\u8bba\u89c6\u89d2"},"content":{"rendered":"
\n
\n
\n
\n

<\/p>\n<\/section>\n

\n
\n
\n
\n
\n
\n

<\/section>\n<\/section>\n
\n
\n

\u5bfc\u8bed<\/strong><\/p>\n<\/section>\n<\/section>\n

\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
\n
\n
\n

\u751f\u7269\u7269\u7406\u6742\u5fd7\uff08Journal of Biological Physics\uff092022\u5e74\u521d\u53d1\u5e03\u7279\u520a\u300a\u666f\u89c2\u7406\u8bba\u5bf9\u751f\u7269\u5b66\u7684\u9769\u547d\u6027\u5f71\u54cd\u300b\u4ee5\u5e86\u795d\u751f\u7269\u7269\u7406\u5148\u9a71Hans Frauenfelder\u7684100\u5c81\u8bde\u8fb0\uff0c\u5176\u4e2d\u6536\u5f55\u4e86\u7f8e\u56fd\u7ebd\u7ea6\u5dde\u7acb\u5927\u5b66\u77f3\u6eaa\u5206\u6821\u6c6a\u52b2\u6559\u6388\u7684\u7efc\u8ff0\u6587\u7ae0\u3002<\/strong>\u6587\u7ae0\u5bf9\u5e73\u8861\u751f\u7269\u7cfb\u7edf\u7684\u666f\u89c2\u7406\u8bba\u548c\u975e\u5e73\u8861\u751f\u7269\u7cfb\u7edf\u7684\u666f\u89c2\u548c\u6d41\u7406\u8bba\uff08landscape and flux theory\uff09\u4f5c\u4e3a\u5168\u5c40\u9a71\u52a8\u529b\u8fdb\u884c\u4e86\u7efc\u8ff0\u3002\u5728\u8be5\u6587\u4e2d\uff0c\u884c\u4e3a\u7684\u6d8c\u73b0\u3001\u71b5\u4e0e\u81ea\u7531\u80fd\u76f8\u5173\u7684\u70ed\u529b\u5b66\uff0c\u4ee5\u53ca\u901f\u7387\u548c\u8def\u5f84\u7684\u52a8\u529b\u5b66\uff0c\u90fd\u5f97\u5230\u5b9a\u91cf\u8bba\u8bc1\u3002\u6587\u7ae0\u8fd8\u8ba8\u8bba\u4e86\u5c42\u7ea7\u5316\u7ec4\u7ec7\u7ed3\u6784\u3002\u4f5c\u8005\u901a\u8fc7\u56fe\u793a\u8bf4\u660e\u4e86\u7406\u8bba\u5728\u5404\u4e2a\u751f\u7269\u5b66\u9886\u57df\u7684\u5e94\u7528\uff0c\u6db5\u76d6\u86cb\u767d\u8d28\u6298\u53e0\u3001\u751f\u7269\u5206\u5b50\u8bc6\u522b\u3001\u7279\u5f02\u6027\u3001\u751f\u7269\u5206\u5b50\u6f14\u5316\u548c\u5e73\u8861\u7cfb\u7edf\u8bbe\u8ba1\u3001\u7ec6\u80de\u5468\u671f\u3001\u5206\u5316\u4e0e\u53d1\u80b2\u3001\u764c\u75c7\u3001\u795e\u7ecf\u7f51\u7edc\u548c\u8111\u529f\u80fd\u3001\u975e\u5e73\u8861\u7cfb\u7edf\u7684\u6f14\u5316\u3001\u57fa\u56e0\u7ec4\u7ed3\u6784\u52a8\u529b\u5b66\u7684\u8de8\u5c3a\u5ea6\u7814\u7a76\u3001\u666f\u89c2\u548c\u6d41\u7684\u5b9e\u9a8c\u91cf\u5316\u548c\u9a8c\u8bc1\u7b49\u3002\u603b\u4f53\u800c\u8a00\uff0c\u8fd9\u4e3a\u666f\u89c2\u548c\u6d41\u7406\u8bba\u89c6\u89d2\u7684\u751f\u7269\u7cfb\u7edf\u884c\u4e3a\u3001\u52a8\u529b\u5b66\u4e0e\u529f\u80fd\uff0c\u63d0\u4f9b\u4e86\u4e00\u4e2a\u5168\u5c40\u7684\u3001\u7269\u7406\u7684\u548c\u5b9a\u91cf\u7684\u56fe\u666f\u3002\u4ee5\u4e0b\u662f\u5bf9\u8be5\u7efc\u8ff0\u6587\u7ae0\u4e2d\u91cd\u8981\u7ae0\u8282\u7684\u6458\u5f55\u7ffb\u8bd1\u548c\u6574\u7406\u3002<\/strong><\/span><\/p>\n


<\/strong><\/span><\/p>\n

\u7814\u7a76\u9886\u57df\uff1a\u975e\u5e73\u8861\u7269\u7406\u5b66\uff0c\u666f\u89c2\u548c\u6d41\u7406\u8bba\uff0c\u751f\u7269\u7269\u7406\uff0c\u7cfb\u7edf\u751f\u7269\u5b66\uff0c\u6d8c\u73b0<\/strong><\/strong><\/span><\/strong><\/span><\/strong><\/span><\/strong><\/strong><\/span><\/strong><\/span><\/strong><\/span><\/strong><\/strong><\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
\n
<\/strong><\/section>\n<\/section>\n
\n

\u6c6a\u52b2<\/span> <\/span>| \u4f5c\u8005<\/strong><\/span><\/p>\n

\u6881\u91d1\u3001\u5218\u57f9\u6e90 <\/span>| <\/strong><\/span>\u7f16\u8bd1<\/strong><\/span><\/p>\n

\u9093\u4e00\u96ea <\/span>| <\/strong><\/span>\u7f16\u8f91<\/strong><\/span><\/p>\n<\/section>\n


<\/section>\n

<\/section>\n
<\/section>\n
\n
\n
\n

\u8bba\u6587\u9898\u76ee\uff1a<\/span><\/p>\n

Perspectives on the landscape and flux theory for describing emergent behaviors of the biological systems<\/span>
<\/p>\n

\u8bba\u6587\u5730\u5740\uff1a<\/span><\/section>\n
https:\/\/link.springer.com\/article\/10.1007\/s10867-021-09586-5<\/span><\/section>\n<\/section>\n<\/section>\n<\/blockquote>\n

 <\/span><\/p>\n

\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\n
\u76ee\u5f55<\/strong><\/section>\n

<\/section>\n
\n
\u4e00\u3001\u5bfc\u8bba<\/span><\/strong><\/section>\n
\u4e8c\u3001\u5e73\u8861\u666f\u89c2<\/span><\/strong><\/section>\n
1. \u86cb\u767d\u8d28\u6298\u53e0<\/span><\/strong><\/section>\n
2. \u7279\u5f02\u6027\u548c\u836f\u7269\u53d1\u73b0<\/span><\/strong><\/section>\n
3. \u86cb\u767d\u8d28\u6f14\u5316\u4e0e\u8bbe\u8ba1<\/span><\/strong><\/section>\n
\u4e09\u3001\u975e\u5e73\u8861\u7cfb\u7edf\u7684\u666f\u89c2\u548c\u6d41\u7406\u8bba<\/span><\/strong><\/section>\n
1. \u975e\u5e73\u8861\u666f\u89c2\u548c\u6d41\u4f5c\u4e3a\u4e00\u822c\u52a8\u529b\u5b66\u7684\u9a71\u52a8\u529b<\/span><\/strong><\/section>\n
2. \u72b6\u6001\u4e4b\u95f4\u7684\u4e3b\u8981\u8def\u5f84\u548c\u52a8\u529b\u5b66<\/span><\/strong><\/section>\n
3. \u4e00\u822c\u7f51\u7edc\u7684\u975e\u5e73\u8861\u70ed\u529b\u5b66\u3001\u71b5\u548c\u81ea\u7531\u80fd<\/span><\/strong><\/section>\n
\u56db\u3001\u975e\u5e73\u8861\u666f\u89c2\u548c\u6d41\u7684\u4f8b\u5b50<\/span><\/strong><\/section>\n
1. \u7ec6\u80de\u5468\u671f<\/span><\/strong><\/section>\n
2. \u7ec6\u80de\u5206\u5316<\/span><\/strong><\/section>\n
3. \u764c\u75c7<\/span><\/strong><\/section>\n
4. \u795e\u7ecf\u7f51\u7edc\u548c\u5927\u8111\u7684\u529f\u80fd<\/span><\/strong><\/section>\n
5. \u8fdb\u5316<\/span><\/strong><\/section>\n
\u4e94\u3001\u4ea4\u53c9\u5c3a\u5ea6\u7684\u4f8b\u5b50<\/span><\/strong><\/section>\n
1. \u57fa\u56e0\u7ec4\u52a8\u529b\u5b66<\/span><\/strong><\/section>\n
2. \u4e0d\u540c\u5c3a\u5ea6\u7684\u5c42\u7ea7\u7ec4\u7ec7<\/span><\/strong><\/section>\n
\u516d\u3001\u666f\u89c2\u548c\u6d41\u7684\u5b9e\u9a8c\u91cf\u5316<\/span><\/strong><\/section>\n
\u4e03\u3001\u5c55\u671b<\/span><\/strong><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

<\/section>\n

<\/section>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u4e00\u3001\u5bfc\u8bba<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n


<\/p>\n

\u6211\u4eec\u5468\u56f4\u7684\u4e16\u754c\u7531\u5927\u91cf\u7684\u539f\u5b50\u548c\u5206\u5b50\u7ec4\u6210\u3002\u867d\u7136\u6211\u4eec\u7406\u89e3\u4e86\u652f\u914d\u8fd9\u4e9b\u7c92\u5b50\u5982\u4f55\u8fd0\u52a8\u7684\u57fa\u672c\u5b9a\u5f8b\uff0c\u4f46\u8fd9\u5e76\u4e0d\u80fd\u81ea\u52a8\u4fdd\u8bc1\uff0c\u6211\u4eec\u7406\u89e3\u4e16\u754c\u5728\u5177\u6709\u5927\u91cf\u57fa\u672c\u5143\u7d20\u7684\u4ecb\u89c2\u548c\u5b8f\u89c2\u5c3a\u5ea6\u4e0a\u5982\u4f55\u5de5\u4f5c\u3002\u4f8b\u5982\uff0c\u6211\u4eec\u4e0d<\/span>\uff08\u5b8c\u5168\uff09<\/span>\u7406\u89e3\u751f\u547d\u662f\u5982\u4f55\u8fd0\u4f5c\u7684\uff0c\u6216\u8005\u5927\u6c14\u662f\u5982\u4f55\u8fd0\u884c\u7684\u3002P.W. Anderson \u6307\u51fa\uff0c\u591a\u8005\u5f02\u4e5f<\/span>\uff08more is different\uff09<\/span>\u3002\u6574\u4f53\u7684\u884c\u4e3a\u53ef\u80fd\u4e0e\u4e2a\u4f53\u884c\u4e3a\u622a\u7136\u4e0d\u540c\u3002\u4e8b\u5b9e\u4e0a\uff0c\u8bb8\u591a\u65b0\u7684\u7279\u5f81\u53ef\u4ee5\u4ece\u533a\u522b\u4e8e\u4e2a\u4f53\u7684\u66f4\u5e95\u5c42\u5143\u7d20\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u4e2d\u6d8c\u73b0\u3002\u56e0\u6b64\uff0c\u4eba\u4eec\u9884\u671f\u81ea\u7136\u6cd5\u5219\u662f\u4f9d\u8d56\u4e8e\u5c3a\u5ea6<\/span>\uff08scale\uff09<\/span>\u7684\u3002\u4e0d\u540c\u5c3a\u5ea6\u4e0a\u53ef\u4ee5\u6709\u4e0d\u540c\u89c4\u5f8b\u3002\u6b63\u662f\u5728\u8fd9\u4e2a\u610f\u4e49\u4e0a\uff0c\u4e07\u7269\u7406\u8bba\u5fc5\u987b\u5305\u62ec\u4e0d\u540c\u5c3a\u5ea6\u4e0a\u7684\u6240\u6709\u6cd5\u5219\uff0c\u800c\u4e0d\u4ec5\u4ec5\u662f\u6700\u5fae\u89c2\u5c42\u9762\u4e0a\u7684\u6cd5\u5219<\/strong>\u3002\u4ece\u8fd9\u4e2a\u89d2\u5ea6\u770b\uff0c\u6211\u4eec\u5df2\u7ecf\u4ed8\u51fa\u5927\u91cf\u52aa\u529b\uff0c\u6765\u7406\u89e3\u7269\u7406\u5b66\u3001\u5929\u6587\u5b66\u3001\u5316\u5b66\u3001\u751f\u7269\u5b66\u3001\u5730\u8d28\u5b66\u3001\u7ecf\u6d4e\u5b66\u548c\u793e\u4f1a\u5b66\u7b49\u4e0d\u540c\u5c3a\u5ea6\u4e0a\u7684\u57fa\u672c\u89c4\u5f8b\u548c\u673a\u5236\u3002\u7406\u89e3\u76f8\u5173\u7684\u590d\u6742\u7cfb\u7edf\u4e0e\u73b0\u8c61\u6240\u9762\u4e34\u7684\u5de8\u5927\u6311\u6218\uff0c\u65e2\u6709\u6982\u5ff5\u4e0a\u7684\uff0c\u4e5f\u6709\u6570\u91cf\u4e0a\u7684\u3002\u4e00\u65b9\u9762\uff0c\u6211\u4eec\u9700\u8981\u53d1\u5c55\u6982\u5ff5\u6765\u6307\u5bfc\u7406\u89e3\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u6211\u4eec\u9700\u8981\u5f00\u53d1\u5b9a\u91cf\u65b9\u6cd5\u548c\u5de5\u5177\u6765\u63a2\u7d22\u548c\u7406\u89e3\u8fd9\u4e9b\u590d\u6742\u7cfb\u7edf\u3002[1-6]<\/span>
<\/section>\n
 <\/span><\/section>\n
Hans Frauenfelder \u6559\u6388\u662f\u7814\u7a76\u8de8\u5c3a\u5ea6\u57fa\u672c\u89c4\u5f8b\u7684\u5148\u9a71[7-10]\u3002\u4ed6\u4e0e\u5408\u4f5c\u8005\u4e13\u6ce8\u4e8e\u751f\u547d\u7684\u57fa\u672c\u529f\u80fd\u5355\u5143\u86cb\u767d\u8d28\uff0c\u5e76\u8bd5\u56fe\u63a2\u7d22\u7ed3\u6784\u4e0e\u52a8\u529b\u5b66\u4e4b\u95f4\u7684\u5173\u7cfb\uff0c\u4ee5\u4e86\u89e3\u86cb\u767d\u8d28\u5982\u4f55\u53d1\u6325\u5176\u529f\u80fd\u3002\u86cb\u767d\u8d28\u662f\u7531\u6210\u5343\u4e0a\u4e07\u4e2a\u539f\u5b50\u7ec4\u6210\u7684\u590d\u6742\u7cfb\u7edf\u3002\u5373\u4f7f\u4e00\u4e2a\u4eba\u5bf9\u5355\u4e2a\u539f\u5b50\u6709\u5f88\u597d\u7684\u4e86\u89e3\uff0c\u4f46\u5bf9\u86cb\u767d\u8d28\u4f5c\u4e3a\u4e00\u4e2a\u6574\u4f53\u7684\u7406\u89e3\u4ecd\u7136\u975e\u5e38\u5177\u6709\u6311\u6218\u6027\u3002\u8bf7\u6ce8\u610f\uff0c\u901a\u5e38\u5f88\u96be\u8ddf\u8e2a\u6bcf\u4e2a\u539f\u5b50\u7684\u52a8\u529b\u5b66\u6765\u4e86\u89e3\u6574\u4e2a\u86cb\u767d\u8d28\u884c\u4e3a[7-10]\u3002\u56e0\u6b64\uff0c\u6211\u4eec\u5e94\u8be5\u5bfb\u627e\u7edf\u8ba1\u65b9\u6cd5\u6765\u7406\u89e3\u8fd9\u4e2a\u590d\u6742\u7684\u7cfb\u7edf\uff0c\u7c7b\u4f3c\u4e8e\u4ece\u7edf\u8ba1\u529b\u5b66\u800c\u975e\u725b\u987f\u529b\u5b66\u6765\u7406\u89e3\u6db2\u4f53\u548c\u6c14\u4f53\u73b0\u8c61\u3002<\/span><\/section>\n
 <\/span><\/section>\n
Frauenfelder \u6559\u6388\u53d1\u5c55\u4e86\u80fd\u91cf\u666f\u89c2\u548c\u5c42\u7ea7\u7ed3\u6784\u7684\u6982\u5ff5\uff0c\u5229\u7528\u914d\u4f53-\u8840\u7ea2\u7d20\u86cb\u767d\u7ed3\u5408<\/span>\uff08\u808c\u7ea2\u86cb\u767d\u548c\u8840\u7ea2\u86cb\u767d\uff09<\/span>\u7684\u4f8b\u5b50\u6765\u89e3\u91ca\u86cb\u767d\u8d28\u7684\u4e0d\u540c\u52a8\u529b\u5b66\u884c\u4e3a[7-10]\u3002\u80fd\u91cf\u666f\u89c2<\/strong>\u662f\u7531\u5355\u4e2a\u539f\u5b50\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u5f62\u6210\u7684\uff0c\u8fd9\u4e9b\u76f8\u4e92\u4f5c\u7528\u901a\u5e38\u4ece\u5fae\u89c2\u7269\u7406\u5b66\u4e2d\u4e86\u89e3\u5230\u3002\u56e0\u6b64\u8fd9\u6539\u53d8\u4e86\u7814\u7a76\u590d\u6742\u7cfb\u7edf\u7684\u6982\u5ff5\u2014\u2014\u4ece\u8ffd\u8e2a\u4e2a\u4f53\u8f68\u8ff9\u5230\u5173\u6ce8\u7cfb\u7edf\u72b6\u6001\u7684\u6f14\u5316\u3002\u7cfb\u7edf\u4f5c\u4e3a\u4e00\u4e2a\u6574\u4f53\u53ef\u4ee5\u7528\u4e0d\u540c\u6743\u91cd\u7684\u72b6\u6001\u6765\u63cf\u8ff0\uff0c\u6bcf\u79cd\u72b6\u6001\u7684\u6743\u91cd\u6839\u636e\u5176\u5e95\u5c42\u666f\u89c2\u7684\u6df1\u5ea6\u6765\u786e\u5b9a\u3002\u4e0d\u540c\u80fd\u91cf\u5c71\u8c37\u6216\u76c6\u5730<\/span>\uff08valley or basins\uff09<\/span>\u4ee3\u8868\u4e86\u86cb\u767d\u8d28\u53ef\u80fd\u7684\u529f\u80fd\u72b6\u6001\uff0c\u8fd9\u4e9b\u529f\u80fd\u72b6\u6001\u7684\u91cd\u8981\u7a0b\u5ea6\u5219\u53d6\u51b3\u4e8e\u5176\u76f8\u5173\u6743\u91cd[7-10]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u6574\u4e2a\u86cb\u767d\u8d28\u72b6\u6001\u7a7a\u95f4\u7684\u80fd\u91cf\u666f\u89c2\u4ecd\u7136\u590d\u6742\uff0c\u8bb8\u591a\u5c71\u8c37\u6216\u76c6\u5730\u88ab\u4e0d\u540c\u9ad8\u5ea6\u7684\u5c4f\u969c\u6240\u9694\u5f00[11,12]\u3002\u5c42\u7ea7\u7ed3\u6784<\/strong>\u4e3a\u8fd9\u4e9b\u72b6\u6001\u7684\u7ec4\u7ec7\u63d0\u4f9b\u4e86\u539f\u5219\u3002\u5728\u4ecb\u89c2\u5c3a\u5ea6\u4e0a\uff0c\u72b6\u6001\u548c\u76f8\u5173\u666f\u89c2\u5c71\u8c37\u7684\u884c\u4e3a\uff0c\u662f\u5176\u4e0b\u4e00\u4e2a\u5c42\u7ea7<\/span>\uff08\u5fae\u89c2\u5c3a\u5ea6\uff09<\/span>\u5355\u4e2a\u5143\u7d20\u4e4b\u95f4\u76f8\u4e92\u4f5c\u7528\u7684\u7ed3\u679c[1-10]\u3002\u5728\u5b8f\u89c2\u5c3a\u5ea6\u4e0a\uff0c\u8fd9\u4e9b\u72b6\u6001\u548c\u76f8\u5173\u666f\u89c2\u5c71\u8c37\u7684\u884c\u4e3a\uff0c\u5bf9\u5e94\u4e8e\u4ecb\u89c2\u5c3a\u5ea6\u4e0a<\/span>\uff08\u5f53\u524d\u611f\u5174\u8da3\u5c3a\u5ea6\u4ee5\u4e0b\u7684\u5c3a\u5ea6\uff09<\/span>\u80fd\u91cf\u5c71\u8c37\u7684\u72b6\u6001\u4e4b\u95f4\u76f8\u4e92\u4f5c\u7528\u7684\u7ed3\u679c\u3002\u56e0\u6b64\uff0c\u6211\u4eec\u53ef\u4ee5\u5728\u5c42\u7ea7\u56fe\u666f\u4e2d\u770b\u5230\uff0c\u666f\u89c2\u7684\u6bcf\u4e2a\u5c42\u6b21\u6216\u6c34\u5e73\u4e0a\uff0c\u529f\u80fd\u72b6\u6001\u662f\u7531\u5176\u4e0b\u7684\u5c42\u7ea7\u4e2d\u5404\u4e2a\u666f\u89c2\u5c71\u8c37\u72b6\u6001\u4e4b\u95f4\u76f8\u4e92\u4f5c\u7528\u7684\u7ed3\u679c\u3002Frauenfelder \u7684\u56e2\u961f\u591a\u5e74\u6765\u5728\u5b9e\u9a8c\u4e0a\u5c55\u793a\u4e86\u86cb\u767d\u8d28\u52a8\u529b\u5b66\u5b58\u5728\u80fd\u91cf\u666f\u89c2\u548c\u76f8\u5173\u5c42\u7ea7\u7ed3\u6784\u7684\u660e\u786e\u8bc1\u636e[13]\u3002\u8fd9\u6307\u5bfc\u4e86\u51e0\u4ee3\u7814\u7a76\u4eba\u5458\u4f7f\u7528\u8fd9\u4e9b\u60f3\u6cd5\u548c\u6982\u5ff5\u6765\u63a2\u7d22\u590d\u6742\u7cfb\u7edf\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u6211\u4eec\u5c06\u5217\u4e3e\u51e0\u4e2a\u4f8b\u5b50\uff0c\u8bf4\u660e\u751f\u7269\u7269\u7406\u5728\u4e30\u5bcc\u548c\u8fdb\u4e00\u6b65\u53d1\u5c55\u8d85\u8d8a\u86cb\u767d\u8d28\u52a8\u529b\u5b66\u7684\u80fd\u91cf\u666f\u89c2\u6982\u5ff5\u548c\u7406\u8bba\u65b9\u9762\u7684\u6700\u65b0\u8fdb\u5c55\u3002\u8fd9\u5305\u62ec\u5728\u5206\u5b50\u5c3a\u5ea6\u4e0a\u7814\u7a76\u86cb\u767d\u8d28\u6298\u53e0\u3001\u751f\u7269\u5206\u5b50\u8bc6\u522b\u3001\u5206\u5b50\u6f14\u5316\u548c\u8bbe\u8ba1\u3001\u57fa\u56e0\u7ec4\u6298\u53e0\u548c\u52a8\u529b\u5b66\uff0c\u4ee5\u53ca\u7814\u7a76\u7ec6\u80de\u5468\u671f\u3001\u5206\u5316\u548c\u53d1\u80b2\u3001\u764c\u75c7\u3001\u8fdb\u5316\u548c\u795e\u7ecf\u7f51\u7edc\u7684\u57fa\u56e0\u548c\u7ec6\u80de\u89c4\u5f8b\u3002<\/span><\/section>\n
 <\/span><\/section>\n
 <\/span><\/section>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u4e8c\u3001\u5e73\u8861\u666f\u89c2<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n


<\/p>\n

\n
\n
\n

1. \u86cb\u767d\u8d28\u6298\u53e0<\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u8981\u7406\u89e3\u86cb\u767d\u8d28\u7684\u529f\u80fd\uff0c\u9996\u5148\u9700\u8981\u77e5\u9053\u76f8\u5173\u7ed3\u6784\u3002\u53ef\u662f\u7ed9\u5b9a\u7ec4\u6210\u86cb\u767d\u8d28\u7684\u6c28\u57fa\u9178\u5e8f\u5217\uff0c\u5982\u4f55\u786e\u5b9a\u86cb\u767d\u8d28\u7684\u7ed3\u6784\uff1f\u5047\u8bbe\u4e00\u4e2a\u6c28\u57fa\u9178\u6b8b\u57fa\u6709 10 \u79cd\u53ef\u80fd\u7684\u6784\u8c61\uff0c\u4e00\u4e2a\u86cb\u767d\u8d28\u7531 100 \u4e2a\u8fd9\u6837\u7684\u6b8b\u57fa\u7ec4\u6210\uff0c\u90a3\u4e48\u86cb\u767d\u8d28\u5c31\u6709 10100<\/sup><\/span> \u79cd\u53ef\u80fd\u7684\u6784\u8c61\u3002\u86cb\u767d\u8d28\u5982\u4f55\u5728\u5982\u6b64\u5927\u91cf\u7684\u6f5c\u5728\u6784\u8c61\u72b6\u6001\u4e2d\u9009\u62e9\u7279\u5b9a\u7684\u5929\u7136\u7ed3\u6784\u72b6\u6001\uff1f <\/span>
<\/section>\n
 <\/span><\/section>\n
\u80fd\u91cf\u666f\u89c2\u7406\u8bba\u63d0\u51fa\uff0c\u4e0d\u540c\u6c28\u57fa\u9178\u6b8b\u57fa\u4e4b\u95f4\u76f8\u4e92\u4f5c\u7528\u7684\u51b2\u7a81\u5bfc\u81f4\u4e86\u6298\u53e0\u666f\u89c2\u7684\u7c97\u7cd9\u6027\uff0c\u800c\u7531\u4e8e\u81ea\u7136\u6f14\u5316\u9009\u62e9\uff0c\u6298\u53e0\u666f\u89c2\u603b\u4f53\u4e0a\u504f\u5411\u4e8e\u81ea\u7136\u6298\u53e0\u72b6\u6001<\/strong>\u3002\u8fd9\u5f62\u6210\u4e86\u4e00\u4e2a\u6f0f\u6597\u72b6\u7684\u666f\u89c2\uff0c\u5bf9\u6297\u86cb\u767d\u8d28\u6298\u53e0\u7684\u5929\u7136\u7ed3\u6784\u72b6\u6001\u7684\u7c97\u7cd9\u5ea6[19]\u3002\u5728\u6298\u53e0\u7684\u65e9\u671f\u9636\u6bb5\uff0c\u591a\u6761\u8def\u5f84\u76f4\u63a5\u671d\u5411\u6298\u53e0\u72b6\u6001\u3002\u5728\u6298\u53e0\u7684\u540e\u671f\u9636\u6bb5\uff0c\u5c40\u90e8\u52bf\u9631\u53ef\u4ee5\u6709\u6548\u5730\u5bfc\u81f4\u6298\u53e0\u7684\u79bb\u6563\u8def\u5f84\u3002\u7531\u4e8e\u5b58\u5728\u504f\u5411\u8d8b\u52bf\uff0c\u5bf9\u5929\u7136\u72b6\u6001\u7684\u641c\u7d22\u53ef\u4ee5\u5927\u5927\u52a0\u901f\u3002 <\/span><\/section>\n
   <\/span><\/section>\n

\u56fe1. \u86cb\u767d\u8d28\u6298\u53e0\u7684\u80fd\u91cf\u6f0f\u6597\u666f\u89c2\u3002\u6f0f\u6597\u6df1\u5ea6\u5bf9\u5e94\u4e8e\u80fd\u91cf\uff0c\u5782\u76f4\u4e8e\u80fd\u91cf\u8f74\u7684\u622a\u9762\u9762\u79ef\u7b49\u4e8e\u6784\u578b\u71b5\u3002\u80fd\u91cf\u548c\u6784\u578b\u71b5\u90fd\u6839\u636e\u86cb\u767d\u8d28\u5c3a\u5bf8\u505a\u4e86\u5f52\u4e00\u5316[19]\u3002\u6839\u636e\u80fd\u91cf\u666f\u89c2\u7406\u8bba\uff0c\u7531\u4e8e\u81ea\u7136\u8fdb\u5316\u9009\u62e9\uff0c\u6298\u53e0\u666f\u89c2\u603b\u4f53\u504f\u5411\u4e8e\u81ea\u7136\u6298\u53e0\u72b6\u6001\u3002<\/span><\/p>\n

 <\/span> <\/span><\/section>\n
\n
\n
\n

2. \u7279\u5f02\u6027\u548c\u836f\u7269\u53d1\u73b0<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u5bf9\u4e8e\u5b9e\u73b0\u751f\u7269\u5b66\u529f\u80fd\u81f3\u5173\u91cd\u8981\u7684\u53e6\u4e00\u4e2a\u6311\u6218\u662f\uff0c\u5982\u4f55\u8bc6\u522b\u4e24\u4e2a\u751f\u7269\u5206\u5b50\u4e4b\u95f4\u7684\u5173\u7cfb\u3002\u4e24\u4e2a\u5173\u952e\u56e0\u7d20\u51b3\u5b9a\u4e86\u8bc6\u522b\uff1a\u4e00\u4e2a\u662f\u4eb2\u548c\u529b\uff0c\u91cf\u5316\u4e24\u4e2a\u5206\u5b50\u4e4b\u95f4\u7ed3\u5408\u7684\u7a33\u5b9a\u6027\uff1b\u53e6\u4e00\u4e2a\u662f\u7279\u5f02\u6027\uff0c\u533a\u5206\u4e00\u4e2a\u9776\u6807\u4e0e\u53e6\u4e00\u4e2a\u9776\u6807\u3002\u5728\u5b9e\u9645\u7684\u836f\u7269\u53d1\u73b0\u8bbe\u8ba1\u4e2d\uff0c\u4eb2\u548c\u529b\u548c\u7279\u5f02\u6027\u7684\u51c6\u786e\u91cf\u5316\uff0c\u662f\u5206\u5b50\u7d27\u5bc6\u7ed3\u5408\u548c\u907f\u514d\u526f\u4f5c\u7528\u6240\u5fc5\u9700\u7684\u3002     <\/span>
<\/section>\n
 <\/span><\/section>\n
\u86cb\u767d\u8d28\u6298\u53e0\u548c\u5206\u5b50\u7ed3\u5408\u7684\u5e95\u5c42\u9a71\u52a8\u529b\u90fd\u662f\u758f\u6c34\u548c\u9759\u7535\u76f8\u4e92\u4f5c\u7528 [15,21,22] \u3002\u7c7b\u4f3c\u4e8e\u86cb\u767d\u8d28\u6298\u53e0\uff0c\u5e95\u5c42\u7684\u7ed3\u5408\u80fd\u666f\u89c2\u81ea\u7136\u5e94\u8be5\u6709\u4e00\u4e2a\u6f0f\u6597\u671d\u5411\u5929\u7136\u7ed3\u5408\u72b6\u6001\u3002\u6f0f\u6597\u72b6\u7684\u7ed3\u5408\u80fd\u666f\u89c2\u63d0\u4f9b\u4e86\u4e00\u4e2a\u91cf\u5316\u7ed3\u5408\u7279\u5f02\u6027\u7684\u6807\u51c6<\/strong>\uff1a\u4e0e\u6f5c\u5728\u7684\u80fd\u91cf\u666f\u89c2\u7c97\u7cd9\u5ea6 \u0394E \u548c\u7531\u71b5 \u0394S \u5ea6\u91cf\u7684\u7cfb\u7edf\u5927\u5c0f\u76f8\u6bd4\uff0c\u80fd\u9699\u6216\u671d\u5411\u5929\u7136\u72b6\u6001\u7684\u504f\u5dee \ud835\udeffE \u5e94\u8be5\u5f88\u5927\u3002\u5b9a\u4e49\u7ed3\u5408\u7279\u5f02\u6027\u7684\u65b0\u65b9\u6cd5\u5df2\u88ab\u7528\u6765\u4ea7\u751f\u4f18\u5316\u7684\u8bc4\u5206\u51fd\u6570\uff0c\u4ee5\u8fbe\u5230\u9ad8\u5ea6\u7684\u4eb2\u548c\u529b\u548c\u7279\u5f02\u6027\uff0c\u5305\u62ec\u5bf9\u914d\u4f53\u7ed3\u5408\u3001\u86cb\u767d\u8d28-\u86cb\u767d\u8d28\u7ed3\u5408\u548c\u86cb\u767d\u8d28-RNA<\/span> (DNA) <\/span>\u7ed3\u5408\u3002\u91cf\u5316\u7279\u5f02\u6027\u7684\u65b0\u65b9\u6cd5\u5df2\u6210\u529f\u5e94\u7528\u4e8e\u836f\u7269\u53d1\u73b0\uff0c\u4ee5\u9274\u5b9a\u9488\u5bf9\u9776\u6807\u5177\u6709\u7279\u5f02\u6027\u7684\u5148\u5bfc\u5316\u5408\u7269\u3002 <\/span><\/section>\n
 <\/span><\/section>\n
<\/section>\n

\u56fe2. \u7279\u5f02\u6027\u6982\u5ff5\u7684\u56fe\u793a\u3002\u5de6\u56fe\uff1a\u4e00\u4e2a\u914d\u4f53\u5bf9\u591a\u4e2a\u5177\u6709\u9ad8\u4eb2\u548c\u529b\u548c\u9ad8\u7279\u5f02\u6027\u53d7\u4f53\uff081\u5bf9Pn<\/sub><\/span>\uff09\u7684\u5e38\u89c4\u7279\u5f02\u6027\u3002\u4e2d\u56fe\uff1a\u6211\u4eec\u5c06\u5177\u6709\u4e00\u4e2a\u5927\u53d7\u4f53\uff08\u5728\u601d\u60f3\u5b9e\u9a8c\u4e2d\u7531\u8bb8\u591a\u5176\u4ed6\u53d7\u4f53\u7ec4\u6210\uff09\u7684\u914d\u4f53\u7684\u56fa\u6709\u7279\u5f02\u6027\u5b9a\u4e49\u4e3a\uff0c\u56fa\u6709\u7ed3\u5408\u6a21\u5f0f\u76f8\u5bf9\u4e8e\u5176\u4ed6\uff081\u5bf9Mn<\/sub><\/span>\uff09\u7684\u533a\u5206\u3002\u53f3\u56fe\uff1a\u53e6\u4e00\u79cd\u5b9a\u4e49\u591a\u4e2a\u914d\u4f53\u5bf9\u4e00\u4e2a\u5177\u6709\u9ad8\u4eb2\u548c\u529b\u548c\u9ad8\u7279\u5f02\u6027\u53d7\u4f53\uff08Nn<\/sub><\/span> vs. M\uff09\u7684\u7279\u5f02\u6027\u7684\u65b9\u6cd5 [23]\u3002<\/span><\/p>\n

   <\/span><\/section>\n
\n
\n
\n

3. \u86cb\u767d\u8d28\u6f14\u5316\u4e0e\u8bbe\u8ba1   <\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u6f0f\u6597\u72b6\u666f\u89c2\u53ef\u7528\u4e8e\u9884\u6d4b\u86cb\u767d\u8d28\u6298\u53e0\u548c\u7ed3\u5408\u7a33\u5b9a\u6027\u4e0e\u529f\u80fd\uff0c\u80cc\u540e\u7684\u539f\u56e0\u5e94\u8be5\u662f\u81ea\u7136\u8fdb\u5316\u3002\u5bf9\u4e8e\u86cb\u767d\u8d28\u6298\u53e0\uff0c\u8fdb\u5316\u53ef\u80fd\u53ea\u63a2\u7d22\u4e86\u6298\u53e0\u548c\u529f\u80fd\u86cb\u767d\u53ef\u4ee5\u8bbf\u95ee\u7684\u72b6\u6001\u7a7a\u95f4\u7684\u4e00\u5c0f\u90e8\u5206\u533a\u57df\u3002<\/span>\u56e0\u6b64\uff0c\u641c\u7d22\u4e0d\u53ef\u80fd\u662f\u5b8c\u5168\u968f\u673a\u7684\u3002\u6839\u636e\u8fbe\u5c14\u6587\u7684\u9002\u8005\u751f\u5b58\u7406\u8bba\uff0c<\/span>\u9664\u4e86\u968f\u673a\u7a81\u53d8\uff0c\u73af\u5883\u5bf9\u86cb\u767d\u8d28\u6f14\u5316\u3001\u9009\u62e9\u53ca\u5176\u76f8\u4e92\u4f5c\u7528\u5fc5\u7136\u5b58\u5728\u9650\u5236\u3002<\/strong><\/section>\n
 <\/span><\/section>\n
\u5728\u56fe3\u4e2d\u53ef\u4ee5\u770b\u5230\uff0c\u5728\u5e8f\u5217\u548c\u6784\u8c61\u7ed3\u6784\u72b6\u6001\u7a7a\u95f4\u4e2d\uff0c\u666f\u89c2\u90fd\u6709\u4e00\u4e2a\u671d\u5411\u5929\u7136\u72b6\u6001\u7684\u8d85\u7ea7\u6f0f\u6597\u3002\u6f0f\u6597\u5e95\u90e8\u662f\u6709\u9650\u5927\u5c0f\u7684\uff0c\u8868\u793a\u4e00\u5b9a\u6570\u91cf\u7684\u5e8f\u5217\u5177\u6709\u76f8\u4f3c\u7684\u6298\u53e0\u7ed3\u6784<\/span>\uff08\u56fe3a, 3b)<\/span>[46]\u3002\u7531\u4e8e\u8fd9\u79cd\u8fdb\u5316\u6f0f\u6597\uff0c\u53ef\u4ee5\u4ea7\u751f\u7a33\u5b9a\u7684\u6298\u53e0\u7ed3\u6784\uff0c\u5177\u6709\u4e0e\u73b0\u6709\u6570\u636e\u4e00\u81f4\u7684\u72ec\u7279\u758f\u6c34\u6838\u5fc3<\/span>\uff08\u56fe3c\uff09<\/span>\u3002\u8fdb\u5316\u6f0f\u6597\u4e5f\u53ef\u4ee5\u4ea7\u751f\u7ed3\u5408\u590d\u5408\u7269\uff0c\u4ece\u8026\u5408\u76f8\u4e92\u4f5c\u7528\u89d2\u5ea6\u800c\u8a00\u7c7b\u4f3c\u4e8e\u5929\u7136\u590d\u5408\u7269<\/span>\uff08\u56fe3d, 3e\uff09<\/span>\u3002<\/span><\/section>\n
 <\/span><\/section>\n
<\/section>\n

\u56fe3. (a) \u5e8f\u5217\u548c\u7ed3\u6784\u7a7a\u95f4\u4e2d\u5929\u7136\u5b58\u5728\u7684\u86cb\u767d\u8d28\u7684\u793a\u610f\u56fe\uff1b(b) \u5e8f\u5217\u548c\u7ed3\u6784\u7a7a\u95f4\u4e2d\u86cb\u767d\u8d28\u8fdb\u5316\u7684\u91cf\u5316\u80fd\u91cf\u666f\u89c2\uff1b(c) \u86cb\u767d\u8d28\u6298\u53e0\u7684\u758f\u6c34\u6838\u5fc3\uff1b(d) \u5206\u5b50\u7ed3\u5408\u3002(e) \u5177\u6709\u5927\u8026\u5408\u503c\u7684\u4f4d\u7f6e\u901a\u8fc7\u63a5\u89e6\uff08\u865a\u7ebf\uff09\u548c\u6210\u952e\uff08\u5b9e\u7ebf\uff09\u5f62\u6210\u7f51\u7edc\u3002<\/span>     <\/span>
<\/p>\n

 <\/span><\/section>\n

\n

<\/section>\n
<\/span><\/section>\n<\/h1>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u4e09\u3001\u975e\u5e73\u8861\u7cfb\u7edf\u7684\u666f\u89c2\u548c\u6d41\u7406\u8bba<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n


<\/p>\n

\n
\n
\n

1. \u975e\u5e73\u8861\u666f\u89c2\u548c\u6d41\u4f5c\u4e3a\u4e00\u822c\u52a8\u529b\u5b66\u7684\u9a71\u52a8\u529b<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u590d\u6742\u7cfb\u7edf\u7684\u52a8\u529b\u5b66\u901a\u5e38\u7531\u9075\u5faa\u4e00\u7ec4\u975e\u7ebf\u6027\u52a8\u529b\u5b66\u65b9\u7a0b\u7684\u9a71\u52a8\u529b\u51b3\u5b9a\uff0c\u5e76\u53ef\u4ee5\u63cf\u8ff0\u4e3a\u4ece\u4e00\u4e2a\u72b6\u6001\u5230\u53e6\u4e00\u4e2a\u72b6\u6001\u7684\u6f14\u5316\u3002\u4f20\u7edf\u4e0a\uff0c\u52a8\u529b\u5b66\u53ca\u76f8\u5173\u7a33\u5b9a\u6027\u7684\u7814\u7a76\u9996\u5148\u53ef\u4ee5\u901a\u8fc7\u8bc6\u522b\u4e0d\u52a8\u70b9<\/span>\uff08fixed point\uff09<\/span>\u5e76\u5728\u4e0d\u52a8\u70b9\u5468\u56f4\u8fdb\u884c\u5c40\u90e8\u7a33\u5b9a\u6027\u5206\u6790\u3002\u7136\u800c\uff0c\u5c40\u90e8\u7a33\u5b9a\u6027\u5206\u6790\u5e76\u4e0d\u4f1a\u7ed9\u51fa\u5173\u4e8e\u5c40\u90e8\u7a33\u5b9a\u72b6\u6001\u4e4b\u95f4\u8054\u7cfb\u7684\u4fe1\u606f\uff0c\u4f46\u8fd9\u5bf9\u4e8e\u7406\u89e3\u72b6\u6001\u4e4b\u95f4\u8f6c\u53d8\u7684\u52a8\u529b\u5b66\u81f3\u5173\u91cd\u8981\u3002\u6b64\u5916\uff0c\u6da8\u843d\u662f\u4e0d\u53ef\u907f\u514d\u7684\u3002\u4e0e\u5176\u9075\u5faa\u7531\u4e8e\u975e\u7ebf\u6027\u548c\u6da8\u843d\u800c\u53d8\u5f97\u4e0d\u53ef\u9884\u6d4b\u7684\u6f14\u5316\u8f68\u8ff9<\/span>\uff08\u5982\u975e\u7ebf\u6027\u6717\u4e4b\u4e07\u65b9\u7a0b\uff09<\/span>\uff0c\u66f4\u5e94\u5173\u6ce8\u9075\u5faa\u7ebf\u6027\u5b9a\u5f8b\u7684\u76f8\u5173\u6982\u7387\u7684\u786e\u5b9a\u6027\u6f14\u5316<\/span>\uff08\u5982 Fokker-Planck \u65b9\u7a0b\u6216\u4e3b\u65b9\u7a0b\uff09<\/span>[69]\u3002\u4e00\u822c\u7684\u52a8\u529b\u7cfb\u7edf\u901a\u5e38\u4e0e\u73af\u5883\u6709\u80fd\u91cf\u3001\u7269\u8d28\u548c\u4fe1\u606f\u4ea4\u6362<\/strong>\u3002\u56e0\u6b64\uff0c\u6211\u4eec\u9700\u8981\u7814\u7a76\u975e\u5e73\u8861\u52a8\u529b\u5b66\uff0c\u4ee5\u7406\u89e3\u5e95\u5c42\u539f\u5219\u548c\u673a\u5236\u3002     <\/span>
<\/section>\n
 <\/span><\/section>\n
\u867d\u7136\u52bf\u80fd\u666f\u89c2\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u7cfb\u7edf\u7684\u6743\u91cd\uff0c\u5b9e\u9645\u7684\u52a8\u529b\u5b66\u5374\u662f\u7531\u666f\u89c2\u548c\u6d41\u5171\u540c\u51b3\u5b9a\u7684\uff0c\u6d41\u901a\u5e38\u5177\u6709\u65cb\u8f6c\u7279\u6027\u3002\u666f\u89c2\u8d8b\u5411\u4e8e\u8ba9\u7cfb\u7edf\u7a33\u5b9a\u5728\u5177\u6709\u8f83\u9ad8\u6982\u7387\u6216\u8f83\u4f4e\u52bf\u80fd\u7684\u72b6\u6001\u6216\u5438\u5f15\u76c6\u5730\uff0c\u800c\u6d41\u63d0\u4f9b\u6765\u81ea\u72b6\u6001\u51c0\u6d41\u5165\u6216\u6d41\u51fa\u7684\u989d\u5916\u529b<\/strong>\u3002\u6211\u4eec\u53ef\u4ee5\u628a\u8fd9\u79cd\u52a8\u529b\u5b66\u7c7b\u6bd4\u4e3a\u4e00\u4e2a\u5e26\u7535\u7c92\u5b50\u5728\u7535\u52bf\u68af\u5ea6\u4e0b\u5728\u7535\u573a\u4e2d\u8fd0\u52a8\uff0c\u5e76\u5728\u4e00\u4e2a\u78c1\u573a\u4e0b\u4ea7\u751f\u87ba\u65cb\u8fd0\u52a8 [5,6,75]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\n
\n
\n

2. \u72b6\u6001\u4e4b\u95f4\u7684\u4e3b\u8981\u8def\u5f84\u548c\u52a8\u529b\u5b66<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u4e3a\u4e86\u7406\u89e3\u52a8\u529b\u5b66\uff0c\u6211\u4eec\u9700\u8981\u627e\u5230\u8fc7\u7a0b\u7684\u8fdb\u884c\u6709\u591a\u5feb\uff0c\u4ee5\u53ca\u5b83\u5b9e\u9645\u5982\u4f55\u53d1\u751f\u3002\u8981\u89e3\u51b3\u8fd9\u4e24\u4e2a\u95ee\u9898\uff0c\u53ef\u4ee5\u91cf\u5316\u72b6\u6001\u4e4b\u95f4\u7684\u4e3b\u8981\u8def\u5f84\uff0c\u5e76\u523b\u753b\u76f8\u5173\u6bd4\u7387\u3002\u5728\u666f\u89c2\u68af\u5ea6\u548c\u6d41\u65cb\u5ea6\u7684\u5171\u540c\u9a71\u52a8\u529b\u4e0b\uff0c\u53ef\u4ee5\u63a8\u5bfc\u51fa\u8def\u5f84\u79ef\u5206\u516c\u5f0f\u3002\u6bcf\u4e00\u6761\u8fde\u63a5\u521d\u59cb\u72b6\u6001\u548c\u6700\u7ec8\u72b6\u6001\u7684\u8def\u5f84 C(t) \u90fd\u6709\u4e00\u4e2a\u6743\u91cd exp(-S(C))<\/span>\uff08S\u662f\u8def\u5f84C\u7684\u4f5c\u7528\u91cf\uff09<\/span>\uff0c\u8fd9\u6761\u8def\u5f84\u7684\u6982\u7387\u7b49\u4e8e\u6240\u6709\u53ef\u80fd\u8def\u5f84\u6743\u91cd\u7684\u603b\u548c\u3002\u4e0d\u540c\u8def\u5f84\u53ef\u4ee5\u6709\u4e0d\u540c\u6743\u91cd\uff0c\u901a\u8fc7\u6700\u5927\u5316\u6743\u91cd\u5c31\u80fd\u8bc6\u522b\u51fa\u4e3b\u8981\u8def\u5f84\u3002\u7531\u4e8e\u6d41\u7684\u65cb\u8f6c\u7279\u6027\uff0c\u975e\u5e73\u8861\u8fc7\u6e21\u6001\u4f1a\u504f\u79bb\u666f\u89c2\u7684\u978d\u70b9\u3002\u4ece\u4e00\u79cd\u72b6\u6001\u5230\u53e6\u4e00\u79cd\u72b6\u6001\u7684\u52a8\u529b\u5b66\u901f\u7387\u7531\u8d77\u59cb\u72b6\u6001\u548c\u975e\u5e73\u8861\u8fc7\u6e21\u6001\u4e4b\u95f4\u7684\u6709\u6548\u52bf\u5792\u51b3\u5b9a\u3002[88]<\/span>
<\/section>\n

<\/span><\/section>\n
<\/section>\n

\u56fe4. 2D \u548c 3D \u7684\u975e\u5e73\u8861\u666f\u89c2\u56fe \uff0c\u66f2\u7ebf\u8868\u793a\u52bf\u80fd\u76c6\u5730\u4e4b\u95f4\u4e0d\u53ef\u9006\u7684\u4e3b\u8981\u8f6c\u53d8\u8def\u5f84 [88] <\/span>  <\/span><\/p>\n

 <\/span><\/p>\n

\n
\n
\n

3. \u4e00\u822c\u7f51\u7edc\u7684\u975e\u5e73\u8861\u70ed\u529b\u5b66\u3001\u71b5\u548c\u81ea\u7531\u80fd<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u9664\u4e86\u975e\u5e73\u8861\u52a8\u529b\u5b66\uff0c\u4e5f\u53ef\u4ee5\u53d1\u5c55\u4e00\u822c\u52a8\u529b\u7cfb\u7edf\u7684\u975e\u5e73\u8861\u6001\u70ed\u529b\u5b66\u6765\u63cf\u8ff0\u5168\u5c40\u6d8c\u73b0\u7684\u6027\u8d28[5,6,75,82,91-94]\u3002\u5728\u6709\u9650\u6da8\u843d\u6761\u4ef6\u4e0b\uff0c\u7cfb\u7edf\u71b5\u7684\u6f14\u5316\u53ef\u4ee5\u5206\u4e3a\u4e24\u4e2a\u90e8\u5206\uff1a\u7cfb\u7edf\u548c\u73af\u5883\u7684\u603b\u71b5\uff0c\u51cf\u53bb\u73af\u5883\u7684\u71b5\u3002\u6839\u636e\u70ed\u529b\u5b66\u7b2c\u4e8c\u5b9a\u5f8b\uff0c\u7cfb\u7edf\u548c\u73af\u5883\u7684\u603b\u4f53\u71b5\u53d8\u5316\u603b\u662f\u5927\u4e8e\u6216\u7b49\u4e8e0\uff0c\u800c\u7cfb\u7edf\u7684\u71b5\u5e76\u603b\u4e0d\u662f\u589e\u52a0\u7684\uff0c\u53e6\u4e00\u65b9\u9762\uff0c\u7cfb\u7edf\u7684\u81ea\u7531\u80fd\u5219\u662f\u6700\u5c0f\u5316\u7684\u3002<\/span>
<\/section>\n
 <\/span><\/section>\n
\u4e8b\u5b9e\u4e0a\uff0c\u71b5\u4ea7\u751f\u7387\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u7ef4\u6301\u52a8\u529b\u7cfb\u7edf\u529f\u80fd\u7684\u70ed\u529b\u5b66\u6210\u672c\u3002\u4ece\u71b5\u4ea7\u751f\u7684\u5b9a\u4e49\u53ef\u4ee5\u770b\u51fa\uff0c\u5b83\u4e0e\u4f5c\u4e3a\u975e\u5e73\u8861\u9a71\u52a8\u529b\u7684\u65cb\u8f6c\u6d41\u76f4\u63a5\u76f8\u5173<\/strong>\u3002\u666f\u89c2\u548c\u6d41\u5bf9\u4e8e\u786e\u5b9a\u52a8\u529b\u7cfb\u7edf\u7684\u5168\u5c40\u6027\u8d28\u90fd\u5f88\u91cd\u8981\u3002\u968f\u7740\u5e95\u5c42\u76f8\u4e92\u4f5c\u7528\u53d8\u5316\uff0c\u53ef\u4ee5\u5bf9\u5e95\u5c42\u666f\u89c2\u5730\u5f62\u548c\u6d41\u8fdb\u884c\u5168\u5c40\u654f\u611f\u5ea6\u5206\u6790\u3002\u8fd9\u6837\u786e\u5b9a\u7684\u5173\u952e\u7c7b\u578b\u7684\u76f8\u4e92\u4f5c\u7528\u5bf9\u7a33\u5b9a\u6027\u548c\u72b6\u6001\u8f6c\u53d8\u52a8\u529b\u5b66\u81f3\u4e3a\u5173\u952e\u3002\u8fd9\u4e3a\u5168\u5c40\u7cfb\u7edf\u7684\u529f\u80fd\u548c\u8bbe\u8ba1\u63d0\u4f9b\u4e86\u53ef\u80fd\u7684\u65b0\u65b9\u6cd5[5,6]\u3002     <\/span><\/section>\n
   <\/span><\/section>\n
 <\/span><\/section>\n

<\/h1>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u56db\u3001\u975e\u5e73\u8861\u666f\u89c2\u548c\u6d41\u7684\u4f8b\u5b50<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n

<\/span>
<\/p>\n

\n
\n
\n
\n

1. \u7ec6\u80de\u5468\u671f<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n


<\/section>\n<\/h2>\n
\u7ec6\u80de\u662f\u751f\u547d\u7684\u57fa\u672c\u5355\u4f4d\uff0c\u53ef\u4ee5\u751f\u957f\u3001\u589e\u6b96\u3001\u5206\u88c2\u548c\u5206\u5316\u3002\u5206\u88c2\u6216\u5faa\u73af\u5bf9\u4e8e\u5c06\u9057\u4f20\u4fe1\u606f\u4f20\u9012\u7ed9\u4e0b\u4e00\u4ee3\u7684\u7ec6\u80de\u751f\u547d\u81f3\u5173\u91cd\u8981 [96-102]\u3002\u7ec6\u80de\u5468\u671f\u8fc7\u7a0b\u53d7\u5230\u5e95\u5c42\u57fa\u56e0\u8c03\u63a7\u7f51\u7edc\u7684\u4e25\u683c\u8c03\u63a7\u3002     <\/span><\/section>\n
 <\/span><\/section>\n
\u7ec6\u80de\u5468\u671f\u901a\u5e38\u88ab\u63cf\u8ff0\u4e3a G1\u3001S\/G2\u3001M \u8fd9\u51e0\u4e2a\u4e0d\u540c\u9636\u6bb5\uff0c\u4e2d\u95f4\u6709\u68c0\u67e5\u70b9\u7528\u4e8e\u68c0\u67e5\u8fdb\u7a0b\u3002\u7ec6\u80de\u5468\u671f\u7684\u666f\u89c2\u6295\u5c04\u5230\u57fa\u56e0\u8868\u8fbe\u4e0a\u663e\u793a\u51fa\u4e00\u4e2a\u4e0d\u89c4\u5219\u7684\u58a8\u897f\u54e5\u8349\u5e3d\u5f62\u72b6 [103]\u3002\u4ece\u666f\u89c2\u68af\u5ea6\u6765\u770b\uff0c\u7cfb\u7edf\u503e\u5411\u4e8e\u88ab\u52bf\u80fd\u8f83\u4f4e\u7684\u73af\u5f62\u5c71\u8c37\u6240\u5438\u5f15\u3002\u6cbf\u7740\u666f\u89c2\u7684\u73af\u5f62\u5c71\u8c37\u6709\u4e09\u4e2a\u5c40\u90e8\u6781\u5c0f\u503c\uff0c\u5bf9\u5e94\u4e8e G1\u3001S\/G2\u3001M \u4e09\u4e2a\u4e0d\u540c\u9636\u6bb5\uff0c\u8fd9\u4e9b\u9636\u6bb5\u7531\u4e8e\u52bf\u80fd\u8f83\u4f4e\uff0c\u505c\u7559\u7684\u673a\u4f1a\u8f83\u9ad8\u3002\u4e0d\u540c\u9636\u6bb5\u4e4b\u95f4\u88ab\u5c40\u90e8\u5c4f\u969c\u5206\u9694\uff0c\u5c4f\u969c\u9876\u90e8\u4f5c\u4e3a\u9636\u6bb5\u4e4b\u95f4\u7684\u5c40\u90e8\u8fc7\u6e21\u72b6\u6001\uff0c\u5bf9\u5e94\u4e8e\u68c0\u67e5\u70b9 [103]\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u4e3a\u4e86\u4f7f\u7ec6\u80de\u5468\u671f\u6cbf\u7740\u4f4e\u52bf\u80fd\u7684\u73af\u5f62\u5c71\u8c37\u632f\u8361\uff0c\u5fc5\u987b\u6709\u53e6\u4e00\u4e2a\u9a71\u52a8\u65cb\u8f6c\u7684\u6d41\u529b\uff0c\u8fd9\u5c31\u662f\u65cb\u5ea6\u6d41\u53d1\u6325\u4f5c\u7528\u7684\u5730\u65b9\u3002\u4e8b\u5b9e\u4e0a\uff0c\u867d\u7136\u666f\u89c2\u68af\u5ea6\u5438\u5f15\u7cfb\u7edf\u4e0b\u964d\u5230\u73af\u5f62\u5c71\u8c37\uff0c\u65cb\u5ea6\u6d41\u9a71\u52a8\u7ec6\u80de\u5468\u671f\u6cbf\u7740\u73af\u5f62\u5c71\u8c37\u632f\u8361<\/strong> [5,6,75,103-105]\u3002\u8fd9\u8868\u660e\u666f\u89c2\u548c\u6d41\u4f5c\u4e3a\u7ec6\u80de\u5468\u671f\u632f\u8361\u7684\u9a71\u52a8\u529b\u90fd\u5fc5\u4e0d\u53ef\u5c11\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u666f\u89c2\u6765\u81ea\u7f51\u7edc\u4e2d\u57fa\u56e0\u4e4b\u95f4\u7684\u8c03\u63a7 [5,6,75,103-105]\u3002\u6d41\u7684\u4f5c\u7528\u529b\u6765\u6e90\u662f ATP\/ADP \u5728\u78f7\u9178\u5316\u548c\u53bb\u78f7\u9178\u5316\u8fc7\u7a0b\u4e2d\u7684\u8425\u517b\u4f9b\u5e94\u548c\u80fd\u91cf\u6cf5 [95]\u3002\u66f4\u591a\u7684\u8425\u517b\u4f9b\u5e94\u5bfc\u81f4\u66f4\u5927\u7684\u6d41\u548c\u66f4\u9ad8\u7684\u901f\u5ea6\uff0c\u4ee5\u53ca\u76f8\u5e72\u6027\u66f4\u597d\u7684\u7ec6\u80de\u5468\u671f\u632f\u8361\u3002\u8fd9\u91cc\u51fa\u73b0\u4e86\u4e00\u4e2a\u6d41\u7684\u9608\u503c\uff0c\u8d85\u8fc7\u8fd9\u4e2a\u9608\u503c\uff0c\u7ec6\u80de\u5468\u671f\u632f\u8361\u5c31\u53ef\u4ee5\u8fdb\u884c\u3002\u8fd9\u8868\u660e\u5355\u7ec6\u80de\u751f\u547d\u8bde\u751f\u9700\u8981\u4e00\u4e2a\u6700\u5c0f\u80fd\u91cf\u3002\u80fd\u91cf\u6cf5\u6216\u9a71\u52a8\u529b\u5bf9\u4e8e\u751f\u547d\u8d77\u6e90\u81f3\u5173\u91cd\u8981 [95,106]\u3002     <\/span><\/section>\n
   <\/span> <\/span><\/section>\n
<\/section>\n

\u56fe5.  \uff08a\uff09\u7ec6\u80de\u5468\u671f\u7684 G1\u3001S\/G2\u3001M \u9636\u6bb5\u548c\u68c0\u67e5\u70b9\u3002\uff08b\uff09\u4e0d\u89c4\u5219\u58a8\u897f\u54e5\u8349\u5e3d\u5f62\u72b6\u7684\u7ec6\u80de\u5468\u671f\u666f\u89c2\u3002\uff08c\uff092D \u666f\u89c2\u56fe\u3002<\/span><\/p>\n

 <\/span><\/section>\n
\n
\n
\n

2. \u7ec6\u80de\u5206\u5316<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u7ec6\u80de\u7684\u5173\u952e\u529f\u80fd\u4e4b\u4e00\u662f\u5206\u5316\uff0c\u539f\u4ee3\u5e72\u7ec6\u80de\u53ef\u4ee5\u53d1\u80b2\u6210\u5177\u6709\u7279\u5b9a\u529f\u80fd\u7684\u5206\u5316\u7ec6\u80de\u3002\u63ed\u793a\u5206\u5316\u7684\u5e95\u5c42\u673a\u5236\u5bf9\u4e8e\u7406\u89e3\u7ec6\u80de\u529f\u80fd\u3001\u7ec4\u7ec7\u5de5\u7a0b\u5b9e\u8df5\u90fd\u5f88\u91cd\u8981 [107-109]\u300220\u4e16\u7eaa50\u5e74\u4ee3\uff0cWaddington \u63d0\u51fa\u4e86\u4e00\u4e2a\u7406\u89e3\u5206\u5316\u548c\u53d1\u80b2\u7684\u56fe\u666f<\/strong>\uff1a\u5047\u5b9a\u5e72\u7ec6\u80de\u5728\u5c71\u9876\uff0c\u5206\u5316\u7ec6\u80de\u5728\u5c71\u8c37\u5e95\u90e8\uff0c\u5206\u5316\u8fc7\u7a0b\u53ef\u4ee5\u770b\u4f5c\u662f\u4e00\u4e2a\u7403\u6cbf\u7740\u5c71\u5761\u6eda\u4e0b\u5230\u5c71\u8c37\u3002<\/span>
<\/section>\n
 <\/span><\/section>\n
Waddington \u7684\u56fe\u666f\u6210\u4e3a\u4e86\u6307\u5f15\u548c\u601d\u8003\u5206\u5316\u4e0e\u53d1\u80b2\u7684\u9690\u55bb[110]\uff0c\u6b64\u540e\u4eba\u4eec\u8bd5\u56fe\u4e3a\u5206\u5316\/\u53d1\u80b2\u63d0\u4f9b\u7269\u7406\u548c\u5b9a\u91cf\u57fa\u7840\u3002\u7814\u7a76\u4eba\u5458\u53d1\u73b0\uff0c\u8d1f\u8d23\u5206\u5316\u7684\u5178\u578b\u6838\u5fc3\u57fa\u56e0\u73af\u8def\u6d89\u53ca\u4e24\u4e2a\u76f8\u4e92\u6291\u5236\u7684\u81ea\u6fc0\u6d3b\u57fa\u56e0[12,78,81,89,111-118]\uff0c\u73af\u8def\u7684\u57fa\u56e0\u8c03\u63a7\u52a8\u529b\u5b66\u53ef\u4ee5\u7528\u76f8\u5e94\u7684\u5e38\u5fae\u5206\u65b9\u7a0b\u63cf\u8ff0\u3002\u666f\u89c2\u53ef\u4ee5\u91cf\u5316\uff0c\u5e76\u4ee5\u57fa\u56e0\u8868\u8fbe\u63cf\u8ff0\u3002\u66f4\u8fdb\u4e00\u6b65\uff0c\u5b9e\u9a8c\u663e\u793a\u5206\u5316\u8fc7\u7a0b\u4e2d\u8c03\u63a7\u5f3a\u5ea6\u4f1a\u53d1\u751f\u53d8\u5316\uff0c\u8fd9\u4e3a\u53d1\u80b2\u63d0\u4f9b\u4e86\u65b9\u5411\u3002\u5bf9\u4e8e\u968f\u7740\u8c03\u63a7\u5f3a\u5ea6\u53d8\u5316\u523b\u753b\u7684\u53d1\u80b2\u8fc7\u7a0b\u7684\u57fa\u56e0\u73af\u8def\u52a8\u529b\u5b66\uff0c\u53ef\u4ee5\u91cf\u5316\u76f8\u5e94\u968f\u673a\u6027\u7684\u7a33\u6001\u6982\u7387\u5206\u5e03\uff0c\u636e\u6b64\u53ef\u4ee5\u91cf\u5316\u5206\u5316\u666f\u89c2\uff0c\u5982\u56fe6\u6240\u793a[78,115]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
<\/section>\n

\u56fe6. \u57fa\u56e0\u8868\u8fbe\uff08x) \u4e0a\u7684\u91cf\u5316 Waddington \u666f\u89c2\uff0c\u6cbf\u7740\u7531\u57fa\u56e0\u8c03\u63a7\u5f3a\u5ea6\u53d8\u5316\u523b\u753b\u7684\u53d1\u80b2\u65b9\u5411\uff08b\uff0c\u5373\u81ea\u6fc0\u6d3b\u548c\u76f8\u4e92\u6291\u5236\u7684\u57fa\u56e0\u8c03\u63a7\u73af\u8def\u7684\u8c03\u63a7\u53d8\u5316\u65b9\u5411\uff09\u7684\u6f14\u5316 [78] \u3002<\/span> <\/span>
<\/p>\n

 <\/span><\/section>\n
\u53ef\u4ee5\u6e05\u695a\u5730\u770b\u5230\uff0c\u5206\u5316\u548c\u53d1\u80b2\u7684\u91cf\u5316\u666f\u89c2\u662f\u57fa\u56e0\u8c03\u63a7\u7684\u7ed3\u679c\uff0c\u8fd9\u4e3a\u521d\u59cb\u7684 Waddington \u56fe\u666f\u63d0\u4f9b\u4e86\u7269\u7406\u57fa\u7840 [78,115]\u3002\u8fd9\u91cc\u5173\u4e8e\u53d1\u80b2\u7684\u91cf\u5316\u666f\u89c2\u4e0e\u57fa\u672c\u7684 Waddington \u666f\u89c2\u76f8\u547c\u5e94\uff0c\u4f46\u6709\u4e00\u4e9b\u660e\u663e\u5dee\u5f02\u3002\u9996\u5148\uff0c\u5e72\u7ec6\u80de\u72b6\u6001\u662f\u5c40\u90e8\u7a33\u5b9a\u7684\uff0c\u5750\u843d\u5728\u5c71\u8c37\u4e2d\uff0c\u800c\u4e0d\u50cf\u521d\u59cb Waddington \u56fe\u666f\u6240\u6697\u793a\u7684\u5728\u5c71\u9876\u4e0a [78,81,89,115,119]\u3002\u5176\u6b21\uff0c\u4ece\u5e72\u7ec6\u80de\u72b6\u6001\u5230\u5206\u5316\u72b6\u6001\uff0c\u4ee5\u53ca\u4ece\u5206\u5316\u72b6\u6001\u91cd\u7f16\u7a0b\u56de\u5230\u5e72\u7ec6\u80de\u72b6\u6001\uff0c\u4e24\u79cd\u9014\u5f84\u662f\u4e0d\u540c\u7684\u3002\u7b2c\u4e09\uff0c\u5206\u5316\u8def\u5f84\u5e76\u4e0d\u6cbf\u7740\u5e95\u5c42\u666f\u89c2\u7684\u68af\u5ea6\u3002\u4e3a\u4e86\u5b8c\u6210\u5206\u5316\u8fc7\u7a0b\uff0c\u9700\u8981\u78f7\u9178\u5316\/\u53bb\u78f7\u9178\u5316\u548c ATP \u6cf5\u6d66\u7b49\u80fd\u91cf\u8f93\u5165\u3002\u8fd9\u63d0\u4f9b\u4e86\u8f93\u5165\u80fd\u6e90\uff0c\u5e76\u4ea7\u751f\u51c0\u6d41<\/span>\uff08net flux\uff09<\/span>\uff0c\u6253\u7834\u4e86\u7ec6\u81f4\u5e73\u8861\u3002\u7531\u4e8e\u52a8\u529b\u5b66\u7684\u9a71\u52a8\u529b\u540c\u65f6\u7531\u666f\u89c2\u548c\u6d41\u51b3\u5b9a\uff0c\u56e0\u6b64\u5206\u5316\u8def\u5f84\u504f\u79bb\u4e86\u539f\u672c\u9884\u671f\u7684\u68af\u5ea6\u8def\u5f84<\/strong>[78,115]\u3002     <\/span><\/section>\n
 <\/span><\/section>\n
\u4eba\u4eec\u8fdb\u4e00\u6b65\u751a\u81f3\u53ef\u4ee5\u53d1\u73b0\u5e73\u5747\u6d41\u7684\u5cf0\u503c\u3001\u71b5\u4ea7\u751f\u7387\u7684\u5cf0\u503c\uff0c\u4ee5\u53ca\u4ece\u5e72\u7ec6\u80de\u72b6\u6001\u76c6\u5730\u5411\u5206\u5316\u72b6\u6001\u76c6\u5730\u5206\u53c9\u7684\u6d8c\u73b0\u8fd9\u4e09\u8005\u4e4b\u95f4\u7684\u5bc6\u5207\u5173\u7cfb\u3002\u8fd9\u7ed9\u51fa\u5e72\u7ec6\u80de\u548c\u5206\u5316\u72b6\u6001\u4e4b\u95f4\u7684\u975e\u5e73\u8861\u76f8\u53d8\u6216\u5206\u53c9\u7684\u7269\u7406\u8d77\u6e90\u3002\u5b83\u8fd8\u4e3a\u7ec6\u80de\u547d\u8fd0\u51b3\u7b56\u63d0\u4f9b\u4e86\u5b9a\u91cf\u6307\u6807\u3002\u5f53\u68af\u5ea6\u529b\u8d8b\u5411\u4e8e\u5438\u5f15\u7cfb\u7edf\u5e76\u7a33\u5b9a\u70b9\u5438\u5f15\u5b50\u65f6\uff0c\u65cb\u8f6c\u7684\u6d41\u4f5c\u7528\u529b\u5374\u8d8b\u5411\u4e8e\u4f7f\u70b9\u5438\u5f15\u5b50\u4e0d\u7a33\u5b9a[78,115]\u3002\u8f83\u9ad8\u7684\u5e73\u5747\u6d41\u4e0e\u8f83\u9ad8\u7684\u975e\u5e73\u8861\u6027\u6709\u5173\uff0c\u56e0\u6b64\u5177\u6709\u8f83\u9ad8\u7684<\/span>\uff08\u7531\u71b5\u4ea7\u751f\u7387\u523b\u753b\u7684\uff09<\/span>\u70ed\u529b\u5b66\u6210\u672c\u3002\u8f83\u9ad8\u7684\u975e\u5e73\u8861\u529b\u548c\u975e\u5e73\u8861\u70ed\u529b\u5b66\u6210\u672c\u53ef\u4ee5\u9a71\u52a8\u70b9\u5438\u5f15\u5b50<\/span>\uff08\u5373\u5e72\u7ec6\u80de\uff09<\/span>\u53d8\u5f97\u4e0d\u7a33\u5b9a\uff0c\u6700\u7ec8\u5bfc\u81f4\u5206\u53c9\u6216\u975e\u5e73\u8861\u76f8\u53d8\uff0c\u5230\u8fbe\u5206\u5316\u6001\uff0c\u53cd\u4e4b\u4ea6\u7136\u3002\u56e0\u6b64\uff0c\u4eba\u4eec\u53ef\u4ee5\u5229\u7528\u975e\u5e73\u8861\u9a71\u52a8\u529b\u548c\u975e\u5e73\u8861\u70ed\u529b\u5b66\u6210\u672c\uff0c\u6765\u9884\u6d4b\u5206\u5316\u548c\u91cd\u7f16\u7a0b\u5206\u53c9\u7684\u8d77\u59cb\u548c\u504f\u79fb[78,115]\u3002     <\/span><\/section>\n
 <\/span><\/section>\n

\n
\n
\n
\n

3. \u764c\u75c7<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n


<\/section>\n<\/h2>\n
\u764c\u75c7\u662f\u4eba\u7c7b\u6b7b\u4ea1\u7684\u4e3b\u8981\u539f\u56e0\u3002\u4f20\u7edf\u4e0a\u8ba4\u4e3a\u764c\u75c7\u7531\u7a81\u53d8\u4ea7\u751f\uff0c\u7136\u800c\u8d8a\u6765\u8d8a\u591a\u7684\u8bc1\u636e\u8868\u660e\uff0c\u8868\u89c2\u9057\u4f20\u5b66\uff0c\u5982\u7ec4\u86cb\u767d\u91cd\u65b0\u4fee\u9970\u3001DNA \u7532\u57fa\u5316\u3001\u7ffb\u8bd1\u540e\u4fee\u9970\u7b49\uff0c\u53ef\u80fd\u626e\u6f14\u975e\u5e38\u91cd\u8981\u7684\u89d2\u8272 [103,113,119,121-130]\u3002\u56e0\u6b64\uff0c\u4ece\u57fa\u56e0\u8c03\u63a7\u7f51\u7edc\u7684\u89d2\u5ea6\u6765\u770b\uff0c\u6700\u597d\u628a\u764c\u75c7\u548c\u6b63\u5e38\u72b6\u6001\u89c6\u4e3a\u6574\u4e2a\u7f51\u7edc\u7684\u72b6\u6001\u3002\u4e0d\u4ec5\u4ec5\u4f9d\u8d56\u4e8e\u7f51\u7edc\u57fa\u56e0\u8282\u70b9<\/span>\uff08\u9057\u4f20\u5b66\uff09<\/span>\u6216\u7f51\u7edc\u8fde\u63a5\u53ca\u57fa\u56e0\u8c03\u63a7<\/span>\uff08\u8868\u89c2\u9057\u4f20\u5b66\uff09<\/span>\uff0c\u800c\u4e14\u5e94\u8003\u8651\u5fae\u73af\u5883\u7684\u53d8\u5316\uff0c\u5982\u8868\u89c2\u9057\u4f20\u5b66\uff0c\u53ef\u80fd\u6270\u4e71\u57fa\u56e0\u8c03\u63a7\uff0c\u4f7f\u4e4b\u671d\u7740\u6b63\u5e38\u6216\u764c\u75c7\u72b6\u6001\u53d1\u5c55<\/span>\uff08\u56fe7\u4e0a\uff09<\/span>\u3002\u6240\u4ee5\uff0c\u5bf9\u6297\u764c\u75c7\u7684\u53ef\u80fd\u7b56\u7565\u5e94\u8be5\u65e2\u5305\u62ec\u8bc6\u522b\u5173\u952e\u57fa\u56e0\uff0c\u4e5f\u5305\u62ec\u786e\u5b9a\u5173\u952e\u8c03\u63a7\u3002\u666f\u89c2\u548c\u6d41\u7406\u8bba\u53ef\u4ee5\u5e2e\u52a9\u786e\u5b9a\u764c\u75c7\u72b6\u6001\uff0c\u4ee5\u53ca\u5173\u952e\u7684\u76f8\u5173\u57fa\u56e0\u548c\u8c03\u63a7\uff0c\u8fd8\u53ef\u4ee5\u5e2e\u52a9\u53d1\u73b0\u764c\u75c7\u5f62\u6210\u548c\u53ef\u80fd\u7684\u9006\u8f6c\u8def\u5f84<\/strong> [131-135]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u4ee5\u80c3\u764c\u4e3a\u4f8b\uff0c\u53ef\u4ee5\u901a\u8fc7\u4e00\u4e2a\u57fa\u56e0\u7f51\u7edc\u6765\u8bf4\u660e\u764c\u75c7\u76f8\u5173\u7684\u8c03\u63a7\u76f8\u4e92\u4f5c\u7528\uff0c\u5982\u56fe6\u5de6\u56fe\u6240\u793a\u3002\u57fa\u4e8e\u57fa\u56e0\u8c03\u63a7\u7f51\u7edc\uff0c\u53ef\u5199\u51fa\u76f8\u5e94\u7684\u57fa\u56e0\u8868\u8fbe\u52a8\u529b\u5b66\u65b9\u7a0b\uff0c\u901a\u8fc7\u89e3\u51b3\u76f8\u5e94\u7684\u968f\u673a Langevin \u65b9\u7a0b\u53ef\u4ee5\u91cf\u5316\u666f\u89c2\u3002\u666f\u89c2\u4e0a\u4f1a\u51fa\u73b0\u4e09\u79cd\u7a33\u5b9a\u72b6\u6001\u5438\u5f15\u5b50\uff1a\u6b63\u5e38\u3001\u80c3\u708e\u548c\u80c3\u764c<\/span>\uff08\u56fe7\u4e0b\uff09<\/span>\uff0c\u6bcf\u79cd\u72b6\u6001\u5438\u5f15\u5b50\u90fd\u5177\u6709\u4e0d\u540c\u7684\u57fa\u56e0\u8868\u8fbe\u8c31 [130]\u3002\u8fd9\u4e9b\u72b6\u6001\u7684\u7a33\u5b9a\u6027\u53ef\u4ee5\u7531\u5b83\u4eec\u4e4b\u95f4\u7684\u8f6c\u6362\u65f6\u95f4\u6765\u89e3\u51b3\uff0c\u53ef\u4ee5\u786e\u5b9a\u6b63\u5e38\u3001\u80c3\u708e\u548c\u80c3\u764c\u72b6\u6001\u4e4b\u95f4\u7684\u4e3b\u8981\u8def\u5f84\u3002\u7ed3\u679c\u8868\u660e\uff0c\u764c\u75c7\u6700\u6709\u53ef\u80fd\u901a\u8fc7\u9996\u5148\u8fbe\u5230\u80c3\u708e\u8fd9\u4e00\u4e2d\u95f4\u6001\u5f62\u6210\uff1b\u5982\u679c\u60c5\u51b5\u6076\u5316\uff0c\u8fd9\u79cd\u80c3\u708e\u7684\u4e2d\u95f4\u6001\u6709\u53ef\u80fd\u8d8a\u8fc7\u5c4f\u969c\uff0c\u8f6c\u53d8\u4e3a\u764c\u75c7\u72b6\u6001\u3002\u5b9a\u91cf\u7814\u7a76\u8bc1\u660e\uff0c\u589e\u52a0\u5e7d\u95e8\u87ba\u6746\u83cc\u611f\u67d3\u7a0b\u5ea6\u53ef\u4ee5\u52a0\u901f\u4ece\u80c3\u708e\u5230\u80c3\u764c\u7684\u8f6c\u53d8\u8fc7\u7a0b\u3002\u901a\u8fc7\u5bf9\u666f\u89c2\u5730\u5f62\u8fdb\u884c\u5168\u5c40\u654f\u611f\u5ea6\u5206\u6790\uff0c\u53ef\u4ee5\u786e\u5b9a\u5173\u952e\u57fa\u56e0\u548c\u8c03\u63a7\u56e0\u5b50\u3002\u8fd9\u4e3a\u80c3\u764c\u5206\u6790\u63d0\u4f9b\u4e86\u65b0\u9014\u5f84\uff0c\u901a\u8fc7\u4fee\u9970\u5173\u952e\u57fa\u56e0\u548c\u5173\u952e\u8c03\u63a7\u63d0\u4f9b\u4e86\u65b0\u7684\u53ef\u80fd\u6cbb\u7597\u7b56\u7565 [5,6,128-130,132- 135]\u3002 <\/span><\/section>\n

<\/span><\/section>\n
   <\/span><\/section>\n
<\/section>\n

\u56fe7. \uff08\u4e0a\uff09\u80c3\u764c\u7684\u8c03\u63a7\u7f51\u7edc\uff0c\u5305\u542b15\u4e2a\u8282\u70b9\u548c72\u4e2a\u8c03\u63a7\uff0c\u5176\u4e2d\u7ea2\u8272\u8868\u793a\u6fc0\u6d3b\u7684\u8c03\u63a7\uff0c\u84dd\u8272\u8868\u793a\u6291\u5236\u7684\u8c03\u63a7\u3002\uff08\u4e0b\uff09\u666f\u89c2\u4e0a\u51fa\u73b0\u4e09\u79cd\u7a33\u5b9a\u72b6\u6001\u5438\u5f15\u5b50\uff1a\u6b63\u5e38\uff08normal\uff09\u3001\u80c3\u708e\uff08Gastritis\uff09\u548c\u80c3\u764c\uff08Gastric cancer\uff09\u3002<\/span><\/p>\n

 <\/span><\/section>\n
\n
\n
\n

4. \u795e\u7ecf\u7f51\u7edc\u548c\u5927\u8111\u7684\u529f\u80fd<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u5728\u5927\u8111\u4e2d\uff0c\u795e\u7ecf\u5143\u901a\u8fc7\u7a81\u89e6\u76f8\u4e92\u8fde\u63a5\u6784\u6210\u795e\u7ecf\u7f51\u7edc[136-138]\u3002\u795e\u7ecf\u7f51\u7edc\u8868\u73b0\u51fa\u5b66\u4e60\u3001\u8bb0\u5fc6\u548c\u51b3\u7b56\u7b49\u8bb8\u591a\u91cd\u8981\u7684\u529f\u80fd [82,91-93]\u3002\u5bf9\u4e8e\u5355\u4e2a\u795e\u7ecf\u5143\uff0cHodgkin-Huxley \u6a21\u578b\u63d0\u4f9b\u4e86\u5b9a\u91cf\u63cf\u8ff0[139]\u3002\u5bf9\u7531\u5927\u91cf\u795e\u7ecf\u5143\u7ec4\u6210\u7684\u795e\u7ecf\u7f51\u7edc\uff0cHopfield \u63d0\u51fa\u8054\u60f3\u8bb0\u5fc6\u6a21\u578b<\/span>\uff08associate memory model\uff09<\/span>\u6765\u7814\u7a76\u5176\u5168\u5c40\u884c\u4e3a [136,139]\u3002\u5bf9\u4e8e\u5bf9\u79f0\u8fde\u63a5\u7684\u795e\u7ecf\u7f51\u7edc\uff0c\u53ef\u4ee5\u91cf\u5316\u5176\u80fd\u91cf\u666f\u89c2\u3002\u5982\u56fe8\u6240\u793a\uff0c\u4ece\u4efb\u4f55\u72b6\u6001\uff0c\u52a8\u529b\u5b66\u6cbf\u7740\u68af\u5ea6\u5411\u4e0b\u79fb\u52a8\u5230\u80fd\u91cf\u666f\u89c2\u4e2d\u6700\u8fd1\u7684\u5438\u5f15\u5b50\u3002\u6bcf\u4e2a\u5438\u5f15\u5b50\u4ee3\u8868\u4ece\u5b66\u4e60\u4e2d\u83b7\u5f97\u7684\u4fe1\u606f\u8bb0\u5fc6\u5b58\u50a8\u3002\u6574\u4e2a\u52a8\u529b\u5b66\u63cf\u8ff0\u4e86\u4ece\u6700\u521d\u7ebf\u7d22\u5f00\u59cb\u7684\u8bb0\u5fc6\u63d0\u53d6\u8fc7\u7a0b\u3002\u7136\u800c\uff0c\u5728\u771f\u6b63\u7684\u795e\u7ecf\u56de\u8def\u4e2d\uff0c\u795e\u7ecf\u8fde\u63a5\u901a\u5e38\u662f\u4e0d\u5bf9\u79f0\u7684\uff0c\u521d\u59cb\u7684 Hopfield \u6a21\u578b\u5e76\u4e0d\u9002\u7528 [91-93]\u3002<\/span>
<\/section>\n
 <\/span><\/section>\n
<\/section>\n

\u56fe8. Hopfield \u795e\u7ecf\u7f51\u7edc\u7684\u8ba1\u7b97\u80fd\u91cf\u51fd\u6570\u666f\u89c2\u793a\u610f\u56fe [93]     <\/span><\/p>\n

 <\/span><\/section>\n
\u8ba4\u8bc6\u5230\u795e\u7ecf\u7f51\u7edc\u662f\u975e\u5e73\u8861\u52a8\u529b\u7cfb\u7edf\uff0c\u53ef\u4ee5\u5e94\u7528\u52bf\u80fd\u548c\u6d41\u666f\u89c2\u7406\u8bba\u7814\u7a76\u795e\u7ecf\u56de\u8def\u52a8\u529b\u5b66\u7684\u5168\u5c40\u884c\u4e3a\u3002Hopfield \u8054\u60f3\u8bb0\u5fc6\u6a21\u578b\u4ec5\u4f7f\u7528\u80fd\u91cf\u666f\u89c2\u6765\u63cf\u8ff0\u795e\u7ecf\u7f51\u7edc\u529f\u80fd\u7684\u5168\u5c40\u884c\u4e3a[4,136]\uff0c\u795e\u7ecf\u7f51\u7edc\u52a8\u529b\u5b66\u5219\u7531\u666f\u89c2\u68af\u5ea6\u548c\u975e\u5e73\u8861\u65cb\u8f6c\u6d41\u5171\u540c\u51b3\u5b9a<\/strong>\u3002\u65cb\u8f6c\u6d41\u53ef\u4ee5\u5f15\u8d77\u87ba\u65cb\u8fd0\u52a8\uff0c\u5bfc\u81f4\u76f8\u5e72\u632f\u8361\uff0c\u8fd9\u5728\u7eaf\u666f\u89c2\u68af\u5ea6\u4f5c\u7528\u4e0b\u7684\u521d\u59cb Hopfield \u6a21\u578b\u4e2d\u4e0d\u4f1a\u51fa\u73b0\u3002\u666f\u89c2\u548c\u6d41\u5bf9\u4e8e\u786e\u5b9a\u8fde\u7eed\u8bb0\u5fc6\u63d0\u53d6\u800c\u975e\u79bb\u6563\u8bb0\u5fc6\u63d0\u53d6\u52a8\u529b\u5b66\u975e\u5e38\u91cd\u8981\u3002\u5f53\u666f\u89c2\u5c06\u7cfb\u7edf\u5438\u5f15\u5230\u632f\u8361\u5438\u5f15\u5b50\u4e0a\u65f6\uff0c\u6d41\u4e3a\u632f\u8361\u5438\u5f15\u5b50\u4e0a\u7684\u76f8\u5e72\u632f\u8361\u6d41\u63d0\u4f9b\u9a71\u52a8\u529b\uff0c\u56e0\u6b64\u5728\u4e0d\u540c\u8bb0\u5fc6\uff08\u632f\u8361\u8def\u5f84\u4e0a\u7684\u6bcf\u4e2a\u70b9\uff09\u4e4b\u95f4\u63d0\u4f9b\u53ef\u80fd\u7684\u8054\u7cfb\u548c\u8fde\u63a5<\/strong>\u3002\u8fd9\u4e5f\u53ef\u4ee5\u63d0\u9ad8\u4fe1\u606f\u5b58\u50a8\u80fd\u529b [91-93]\u3002 <\/span><\/section>\n
   <\/span><\/section>\n
\u5bf9\u4e8e\u5feb\u901f\u773c\u52a8<\/span>\uff08REM\uff09<\/span>\u7761\u7720\u5468\u671f\u6a21\u578b\uff0c\u4f7f\u7528\u666f\u89c2\u548c\u6d41\u7406\u8bba\u5e76\u8fdb\u884c\u5168\u5c40\u654f\u611f\u5ea6\u5206\u6790\uff0c\u53ef\u4ee5\u627e\u5230\u4e00\u4e9b\u529f\u80fd\u7684\u5173\u952e\u56e0\u7d20\uff0c\u5982\u4e59\u9170\u80c6\u78b1<\/span>\uff08Ach\uff09<\/span>\u548c\u53bb\u7532\u80be\u4e0a\u817a\u7d20\u7684\u91ca\u653e\u3002\u7814\u7a76\u53d1\u73b0\uff0c\u6d41\u5bf9 REM \u7761\u7720\u8282\u5f8b\u7684\u7a33\u5b9a\u6027\u548c\u901f\u5ea6\u90fd\u975e\u5e38\u91cd\u8981\u3002\u975e\u5e73\u8861\u666f\u89c2\u548c\u6d41\u7406\u8bba\u4e5f\u88ab\u5e94\u7528\u4e8e\u5927\u8111\u51b3\u7b56\u3001\u6050\u60e7\u53cd\u5e94\u3001\u5de5\u4f5c\u8bb0\u5fc6\u3001\u5e15\u91d1\u68ee\u75c7\u7684\u5927\u8111\u529f\u80fd [91-93,140,141]\u3002<\/span><\/section>\n
 <\/span><\/section>\n

\n
\n
\n
\n

5. \u8fdb\u5316<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n


<\/section>\n<\/h2>\n
\u751f\u7269\u5b66\u7531\u8fdb\u5316\u6240\u51b3\u5b9a\u3002\u8fbe\u5c14\u6587\u9996\u5148\u63d0\u51fa\u4e86\u9002\u8005\u751f\u5b58\u7684\u81ea\u7136\u9009\u62e9\u539f\u7406\u3002\u4e4b\u540e Fisher \u548c Wright \u4e24\u4f4d\u79d1\u5b66\u5bb6\u5bf9\u8fbe\u5c14\u6587\u601d\u60f3\u8fdb\u884c\u4e86\u91cf\u5316 [143]\u3002Fisher \u5173\u4e8e\u81ea\u7136\u9009\u62e9\u7684\u57fa\u672c\u5b9a\u7406\u8868\u660e\uff0c\u5e73\u5747\u9002\u5e94\u5ea6\u7684\u589e\u52a0\u7387\u7b49\u4e8e\u5176\u9057\u4f20\u65b9\u5dee[142]\u3002Wright \u63d0\u51fa\u4e86\u9002\u5e94\u5ea6\u666f\u89c2<\/strong><\/span>\uff08fitness landscape\uff09<\/span>\u7684\u6982\u5ff5\uff0c\u5c06\u8fdb\u5316\u9002\u5e94\u8fc7\u7a0b\u91cf\u5316\u4e3a\u4e00\u4e2a\u722c\u5c71\u8fc7\u7a0b\uff0c\u76f4\u5230\u8fbe\u5230\u5c40\u90e8\u9002\u5e94\u5ea6\u5cf0\u503c\uff0c\u5982\u56fe9\u6240\u793a\u3002Wright \u7684\u9002\u5e94\u5ea6\u666f\u89c2\u548c Fisher \u7684\u81ea\u7136\u9009\u62e9\u57fa\u672c\u5b9a\u7406\u88ab\u5e7f\u6cdb\u7528\u4e8e\u5c06\u8fdb\u5316\u89e3\u91ca\u4e3a\u9002\u5e94\u6027\u6700\u5927\u5316\u3002\u8fd9\u4e9b\u7406\u8bba\u9002\u7528\u4e8e\u7269\u79cd\u5185\u6216\u7269\u79cd\u95f4\u76f8\u4e92\u4f5c\u7528\u53ef\u4ee5\u5ffd\u7565\u7684\u60c5\u51b5<\/span>\uff08\u7b49\u4f4d\u57fa\u56e0\u9891\u7387\u72ec\u7acb\u9009\u62e9\uff09<\/span>[146]\u3002<\/span><\/section>\n

<\/section>\n
<\/section>\n

\u56fe9. \u9002\u5e94\u5ea6\u666f\u89c2\u7406\u8bba\u5c06\u8fdb\u5316\u9002\u5e94\u8fc7\u7a0b\u91cf\u5316\u4e3a\u4e00\u4e2a\u722c\u5c71\u8fc7\u7a0b\uff0c\u76f4\u5230\u8fbe\u5230\u5c40\u90e8\u9002\u5e94\u5ea6\u5cf0\u503c \uff08A\uff09\u800c\u666f\u89c2\u548c\u6d41\u7406\u8bba\u5c06\u8fdb\u5316\u9002\u5e94\u8fc7\u7a0b\u91cf\u5316\u4e3a\u4e00\u4e2a\u87ba\u65cb\u4e0b\u964d\u8fc7\u7a0b\uff0c\u76f4\u5230\u8fbe\u5230\u52bf\u80fd\u8c37\u3002\u8fd9\u4e2a\u8c37\u53ef\u4ee5\u662f\u4e00\u4e2a\u5c01\u95ed\u73af \uff08B\uff09<\/span><\/p>\n

 <\/span><\/section>\n
\u7136\u800c\uff0c\u7269\u79cd\u5185\u6216\u7269\u79cd\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u53ef\u80fd\u5bfc\u81f4\u7b49\u4f4d\u57fa\u56e0\u9891\u7387\u4f9d\u8d56\u7684\u9009\u62e9\u3002\u5728\u8fd9\u79cd\u4e00\u822c\u60c5\u51b5\u4e0b\uff0c\u8fdb\u5316\u52a8\u529b\u5b66\u4e0d\u518d\u9075\u5faa\u5e73\u5747\u9002\u5e94\u5ea6\u68af\u5ea6\u8fbe\u5230\u9002\u5e94\u5ea6\u9876\u5cf0\uff0c\u800c\u662f\u8fdb\u5165\u4e00\u4e2a\u65e0\u9650\u5faa\u73af\u3002\u8fd9\u79cd\u8fdb\u5316\u4e2d\u7684\u5faa\u73af\u884c\u4e3a\u88ab\u79f0\u4e3a\u7ea2\u7687\u540e\u5047\u8bf4\uff0c\u5373\u4e0d\u540c\u7269\u79cd\u4e4b\u95f4\u7684\u751f\u7269\u76f8\u4e92\u4f5c\u7528\u53ef\u80fd\u5bfc\u81f4\u4e00\u4e9b\u7269\u79cd\u65e0\u4f11\u6b62\u7684\u8fdb\u5316\uff0c\u5373\u4f7f\u8fdb\u5316\u8fbe\u5230\u4e86\u6700\u4f18\u72b6\u6001\u3002\u5171\u8fdb\u5316\u7cfb\u7edf\u53ef\u80fd\u8fdb\u5165\u5faa\u73af\u3002\u52bf\u80fd\u548c\u6d41\u666f\u89c2\u7406\u8bba\u53ef\u4ee5\u4e3a\u7ea2\u7687\u540e\u5047\u8bf4\u63d0\u4f9b\u7269\u7406\u57fa\u7840\u548c\u5b9a\u91cf\u89e3\u91ca\u3002\u751f\u7269\u76f8\u4e92\u4f5c\u7528\u4ea7\u751f\u7684\u65cb\u8f6c\u6d41\u652f\u6301\u5373\u4f7f\u8fbe\u5230\u8fdb\u5316\u6700\u4f18\u72b6\u6001\u65f6\u4ecd\u5b58\u5728\u9057\u4f20\u65b9\u5dee<\/strong>\uff0c\u8fdb\u5316\u8fc7\u7a0b\u4ecd\u7136\u6301\u7eed\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u4f20\u7edf\u7684 Wright \u68af\u5ea6\u9002\u5e94\u5ea6\u666f\u89c2\u4e0d\u8db3\u4ee5\u786e\u5b9a\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66 [5,6,76,82]\u3002\u7136\u800c\uff0c\u674e\u4e9a\u666e\u8bfa\u592b\u51fd\u6570\u4f5c\u4e3a\u4e00\u79cd\u5185\u5728\u7684\u81ea\u9002\u5e94\u666f\u89c2\uff0c\u53ef\u4ee5\u91cf\u5316\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66\u7684\u5168\u5c40\u7a33\u5b9a\u6027\u3002\u8fdb\u5316\u52a8\u529b\u5b66\u7531\u666f\u89c2\u548c\u65cb\u8f6c\u6d41\u5171\u540c\u51b3\u5b9a\u3002\u65cb\u8f6c\u6d41\u53ef\u4ee5\u6765\u6e90\u4e8e\u7269\u79cd\u5185\u90e8\u548c\u7269\u79cd\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u3001\u7a81\u53d8\u3001\u91cd\u7ec4\u548c\u5f02\u4f4d\u663e\u6027<\/span>\uff08epistasis\uff09<\/span>\u3002\u8fdb\u5316\u7684\u5185\u7980\u80fd\u3001\u71b5\u548c\u81ea\u7531\u80fd\u53ef\u4ee5\u5b9a\u4e49\uff0c\u76f8\u5173\u7684\u975e\u5e73\u8861\u6001\u70ed\u529b\u5b66\u53ef\u4ee5\u5efa\u7acb\u8d77\u6765[5,6,76,82]\u3002\u5185\u5728\u666f\u89c2\u548c\u81ea\u7531\u80fd\u90fd\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u8fdb\u5316\u7684\u5168\u5c40\u7a33\u5b9a\u6027\u548c\u7a33\u5065\u6027\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u8fdb\u5316\u7684\u666f\u89c2\u548c\u6d41\u7406\u8bba\u63ed\u793a\u4e86\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66\u7684\u51e0\u4e2a\u622a\u7136\u4e0d\u540c\u7684\u6027\u8d28\uff0c\u4e0d\u540c\u4e8e Wright-Fisher \u8fdb\u5316\u7406\u8bba [142,144]\u3002\u7531\u4e8e\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66\u7684\u9a71\u52a8\u529b\u4e2d\u5b58\u5728\u6d41\u7684\u6210\u5206\uff0c\u5e73\u5747\u9002\u5e94\u5ea6\u666f\u89c2\u53ca\u5176\u5cf0\u503c\u53ef\u80fd\u4e0e\u6982\u7387\u666f\u89c2\u53ca\u5176\u5cf0\u503c\u4e0d\u4e00\u81f4\u3002\u8fd9\u610f\u5473\u7740\u5e73\u5747\u9002\u5e94\u5ea6\u53ef\u80fd\u4e0d\u662f\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66\u7684\u7ec8\u6781\u547d\u8fd0\u3002\u5e73\u5747\u9002\u5e94\u5ea6\u666f\u89c2\u548c\u6982\u7387\u666f\u89c2\u7684\u5dee\u5f02\uff0c\u53ef\u80fd\u6765\u81ea\u7269\u79cd\u5185\u548c\u7269\u79cd\u95f4\u7684\u76f8\u4e92\u4f5c\u7528<\/span>\uff08\u7b49\u4f4d\u57fa\u56e0\u9891\u7e41\u4f9d\u8d56\u7684\u9009\u62e9\uff09<\/span>\u3001\u7a81\u53d8\u3001\u91cd\u7ec4\u548c\u5f02\u4f4d\u663e\u6027\u7b49\u3002\u5bf9\u4e8e\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66\uff0c\u76ee\u6807\u662f\u8fbe\u5230\u6982\u7387\u5cf0\u503c\u800c\u4e0d\u662f\u9002\u5e94\u5ea6\u5cf0\u503c\u3002\u666f\u89c2\u548c\u6d41\u7406\u8bba\u5df2\u5e94\u7528\u4e8e\u66f4\u4e00\u822c\u7684\u591a\u7b49\u4f4d\u57fa\u56e0\u3001\u591a\u4f4d\u70b9\u8fdb\u5316\u52a8\u529b\u5b66\uff0c\u4e3a\u4e00\u822c\u7684\u8fdb\u5316\u52a8\u529b\u5b66\u63d0\u4f9b\u7406\u8bba\u57fa\u7840 [5,6,76,82]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
 <\/span><\/section>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u4e94\u3001\u4ea4\u53c9\u5c3a\u5ea6\u7684\u4f8b\u5b50<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n


<\/p>\n

\n
\n
\n

1. \u57fa\u56e0\u7ec4\u52a8\u529b\u5b66<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n


<\/section>\n
\u6211\u4eec\u56de\u987e\u4e86\u7406\u89e3\u5206\u5b50\u6c34\u5e73\u548c\u7ec6\u80de\u6c34\u5e73\u7684\u52a8\u529b\u5b66\u548c\u529f\u80fd\u7684\u4e00\u4e9b\u52aa\u529b\u3002\u4f46\u662f\uff0c\u8fd9\u4e24\u79cd\u65b9\u6cd5\u4e4b\u95f4\u7f3a\u5c11\u8054\u7cfb\u3002\u4e00\u65b9\u9762\uff0c\u5206\u5b50\u52a8\u529b\u5b66\u53ef\u4ee5\u901a\u8fc7\u539f\u5b50\u6c34\u5e73\u7684\u6a21\u62df\u6765\u5efa\u6a21\u3002\u53e6\u4e00\u65b9\u9762\uff0c\u7ec6\u80de\u6c34\u5e73\u52a8\u529b\u5b66\u548c\u529f\u80fd\u7531\u6d53\u5ea6\u6216\u8868\u8fbe\u6c34\u5e73\u7684\u5316\u5b66\u53cd\u5e94\u52a8\u529b\u5b66\u5efa\u6a21\u3002\u4e8b\u5b9e\u4e0a\uff0c\u7ec6\u80de\u7f51\u7edc\u7684\u8fd9\u4e9b\u8868\u8fbe\u6c34\u5e73\u52a8\u529b\u5b66\u662f\u5e95\u5c42\u7684\u57fa\u56e0\u548c\u86cb\u767d\u8d28\u5206\u5b50\u52a8\u529b\u5b66\u7684\u53cd\u6620\u3002     <\/strong><\/span><\/section>\n
 <\/span><\/section>\n
\u7531\u4e8e\u6280\u672f\u7684\u8fc5\u901f\u53d1\u5c55\uff0c\u7279\u522b\u662f Hi-C \u65b9\u6cd5\uff0c\u67d3\u8272\u4f53\u548c\u57fa\u56e0\u7ec4\u7684\u7cfb\u7efc\u5e73\u5747\u7ed3\u6784\u53ef\u4ee5\u901a\u8fc7\u5355\u4e2a\u5143\u4ef6\u4e4b\u95f4\u7684\u63a5\u89e6\u56fe<\/span>\uff08contact map\uff09<\/span>\u5f97\u5230 [147-152]\u3002\u4eba\u4eec\u53ef\u4ee5\u4f7f\u7528 Hi-C \u63a5\u89e6\u4fe1\u606f\u6765\u63a8\u65ad\u57fa\u56e0\u7ec4\u7cfb\u7efc\u5e73\u5747\u7ed3\u6784\u3002\u7136\u800c\uff0cHi-C \u6570\u636e\u53ea\u80fd\u63d0\u4f9b\u4e00\u4e2a\u7ec6\u80de\u72b6\u6001\u4e0b\u7684\u57fa\u56e0\u7ec4\u7ec4\u7ec7\uff0c\u5728\u4e24\u4e2a\u7ec6\u80de\u72b6\u6001\u8f6c\u6362\u8fc7\u7a0b\u4e2d\uff0c\u57fa\u56e0\u7ec4\u6216\u67d3\u8272\u4f53\u7ed3\u6784\u53d8\u5316\u7684\u4fe1\u606f\u5c1a\u672a\u80fd\u83b7\u5f97\uff0c\u800c\u8fd9\u5bf9\u4e8e\u7ec6\u80de\u5206\u5316\u548c\u53d1\u80b2\u3001\u764c\u75c7\u5f62\u6210\u3001\u7ec6\u80de\u5468\u671f\u7b49\u529f\u80fd\u5374\u81f3\u5173\u91cd\u8981\u3002\u5bf9\u7ec6\u80de\u547d\u8fd0\u53d8\u5316\u548c\u51b3\u7b56\u4e2d\u7ed3\u6784\u8f6c\u53d8\u7684\u5fae\u89c2\u63cf\u8ff0\u975e\u5e38\u9700\u8981[12,153-155]\u3002 <\/span><\/section>\n

<\/section>\n
\u57fa\u56e0\u7ec4\u662f\u5de8\u5927\u7684\uff0c\u6d89\u53ca 109<\/sup> \u4e2a\u78b1\u57fa\u5bf9\u3002\u6211\u4eec\u9884\u671f\u4e24\u79cd\u7ec6\u80de\u72b6\u6001\u4e4b\u95f4\u7684\u5c4f\u969c\u662f\u5de8\u5927\u7684\u3002\u90a3\u4e48\u81ea\u7136\u60c5\u51b5\u4e0b\uff0c\u7ec6\u80de\u72b6\u6001\u7684\u8f6c\u53d8\u8fc7\u7a0b\u662f\u5982\u4f55\u53d1\u751f\u7684\u5462\uff1f\u770b\u8d77\u6765\u6240\u6709\u8fd9\u4e9b\u7ec6\u80de\u547d\u8fd0\u51b3\u7b56\u8fc7\u7a0b\u90fd\u6d89\u53ca\u78f7\u9178\u5316\/\u53bb\u78f7\u9178\u5316\u8fc7\u7a0b\uff0c\u6709\u8bb8\u591a ATP \u80fd\u91cf\u6cf5\u3002\u8fd9\u8868\u660e\u80fd\u91cf\u6fc0\u6d3b\u662f\u4e0d\u53ef\u907f\u514d\u7684\uff0c\u53ef\u7528\u4e8e\u4fc3\u8fdb\u7ec6\u80de\u72b6\u6001\u8f6c\u53d8\u3002\u8fd9\u50ac\u751f\u4e86\u7528\u4e8e\u91cf\u5316\u7ec6\u80de\u547d\u8fd0\u8f6c\u53d8\u8fc7\u7a0b\u7684\u666f\u89c2\u6fc0\u53d1-\u5f1b\u8c6b\u6a21\u578b<\/strong><\/span>\uff08landscape excitation-relaxation model\uff09<\/span>\u3002\u5982\u56fe10\u6240\u793a\u3002\u4e24\u4e2a\u7ec6\u80de\u7684\u547d\u8fd0\u7531\u5404\u81ea\u80fd\u91cf\u666f\u89c2\u7684\u4e24\u4e2a\u76c6\u5730\u63cf\u8ff0\u3002ATP \u80fd\u91cf\u6cf5\u63d0\u4f9b\u4e86\u4ece\u4e00\u4e2a\u521d\u59cb\u666f\u89c2\u8df3\u5230\u53e6\u4e00\u4e2a\u666f\u89c2\u7684\u673a\u4f1a\uff0c\u7136\u540e\u5f1b\u8c6b\u5230\u5438\u5f15\u76c6\u5730\uff0c\u800c\u4e0d\u662f\u76f4\u63a5\u8de8\u8d8a\u9ad8\u5230\u65e0\u6cd5\u903e\u8d8a\u7684\u5c4f\u969c\u3002\u8fd9\u6a21\u62df\u4e86\u7ec6\u80de\u547d\u8fd0\u51b3\u7b56\u4e2d\u72b6\u6001\u8f6c\u53d8\u7684\u81ea\u7136\u53d1\u751f\u8fc7\u7a0b[12,153,154]\u3002     <\/span><\/section>\n
 <\/span><\/section>\n
<\/section>\n
 \u56fe10. \u7ec6\u80de\u547d\u8fd0\u51b3\u7b56\u8fc7\u7a0b\u4e2d\u7684\u666f\u89c2\u6fc0\u53d1-\u5f1b\u8c6b\u6a21\u578b\u3002<\/span><\/span><\/section>\n
 <\/span><\/section>\n
\u4eba\u4eec\u5c06\u8be5\u6a21\u578b\u5e94\u7528\u4e8e\u764c\u75c7\u548c\u53d1\u80b2\uff0c\u63a2\u7d22\u4e86\u591a\u80fd\u80da\u80ce\u5e72\u7ec6\u80de<\/span>\uff08ESC\uff09<\/span>\u3001\u5206\u5316\u7684\u6b63\u5e38\u7ec6\u80de\u548c\u764c\u7ec6\u80de\u4e4b\u95f4\u7ec6\u80de\u72b6\u6001\u8f6c\u53d8\u8fc7\u7a0b\u4e2d\u7684\u67d3\u8272\u4f53\u7ed3\u6784\u52a8\u529b\u5b66\uff0c\u5982\u56fe11\u6240\u793a\u3002\u8003\u8651\u4e86\u5206\u5316\u3001\u91cd\u7f16\u7a0b\u548c\u764c\u75c7\u5f62\u6210\u8fc7\u7a0b\u4e2d\u6d89\u53ca\u7684\u7ec6\u80de\u547d\u8fd0\u76846\u79cd\u8f6c\u53d8\u3002\u7814\u7a76\u53d1\u73b0\uff0c\u5728\u5411\u5e72\u7ec6\u80de\u6216\u6b63\u5e38\u7ec6\u80de\u7684\u72b6\u6001\u8f6c\u53d8\u8fc7\u7a0b\u4e2d\uff0c\u901a\u8def\u53ef\u80fd\u5408\u5e76\uff1b\u4f46\u764c\u75c7\u5f62\u6210\u901a\u8def\u6ca1\u6709\u6765\u81ea\u6b63\u5e38\u7ec6\u80de\u72b6\u6001\u6216\u5e72\u7ec6\u80de\u72b6\u6001\u7684\u5408\u5e76\u3002\u8fd9\u8bf4\u660e\u764c\u75c7\u7684\u5f62\u6210\u53ef\u80fd\u6d89\u53ca\u591a\u79cd\u901a\u8def\u3002\u57fa\u56e0\u7ec4\u6a21\u578b\u53ef\u4ee5\u4ece\u52a8\u6001\u67d3\u8272\u4f53\u7ed3\u6784\u7684\u89d2\u5ea6\uff0c\u4e3a\u7ec6\u80de\u5206\u5316\u548c\u764c\u75c7\u5f62\u6210\u63d0\u4f9b\u5fae\u89c2\u5206\u5b50\u6c34\u5e73\u63cf\u8ff0<\/strong>\u3002\u8fd9\u53ef\u4ee5\u4fc3\u8fdb\u5bf9\u7ec6\u80de\u547d\u8fd0\u51b3\u7b56\u8fc7\u7a0b\u4e2d\u5e95\u5c42\u5206\u5b50\u673a\u5236\u7684\u7406\u89e3[12,153-155]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
<\/section>\n

\u56fe11. \u4ece\u67d3\u8272\u4f53\u7ed3\u6784\u52a8\u529b\u5b66\u89d2\u5ea6\uff0c\u8bf4\u660e\u4e86\u80da\u80ce\u5e72\u7ec6\u80de\uff08ESC\uff09\u3001\u6b63\u5e38\u7ec6\u80de\u548c\u764c\u7ec6\u80de\u4e4b\u95f4\u76846\u79cd\u7ec6\u80de\u72b6\u6001\u8f6c\u53d8\u8fc7\u7a0b\u3002\u4ece\u9876\u90e8\u5230\u5e95\u90e8\u7684\u5782\u76f4\u7bad\u5934\u8868\u793a\u67d3\u8272\u4f53\u538b\u7f29\u7684\u7a0b\u5ea6 [154]\u3002<\/span> <\/span><\/p>\n

 <\/span> <\/span><\/section>\n
\n
\n
\n

2. \u4e0d\u540c\u5c3a\u5ea6\u7684\u5c42\u7ea7\u7ec4\u7ec7<\/span><\/strong><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n


<\/p>\n<\/section>\n

\u6b63\u5982\u6211\u4eec\u6240\u770b\u5230\u7684\uff0c\u5927\u5c3a\u5ea6\u7684\u6d8c\u73b0\u884c\u4e3a\u901a\u5e38\u662f\u5c0f\u5c3a\u5ea6\u5143\u7d20\u76f8\u4e92\u4f5c\u7528\u7684\u7ed3\u679c\u3002\u8f83\u5927\u5c3a\u5ea6\u7684\u6d8c\u73b0\u884c\u4e3a\u4e0e\u8f83\u5c0f\u5c3a\u5ea6\u7684\u884c\u4e3a\u53ef\u80fd\u6709\u5f88\u5927\u4e0d\u540c\u3002Hans \u548c\u8be5\u9886\u57df\u7684\u5176\u4ed6\u79d1\u5b66\u5bb6\u63d0\u51fa\u590d\u6742\u7cfb\u7edf\u7684\u5c42\u7ea7\u7ec4\u7ec7<\/strong><\/span>\uff08hierarchical organization\uff09<\/span>[1,2,4,9,74,156] \uff0c\u5305\u62ec\u5bf9\u79f0\u6027\u7834\u7f3a\u3001\u5206\u5c94\u548c\u6d8c\u73b0\u7684\u6982\u5ff5<\/strong>\u3002\u8fd9\u4e9b\u6982\u5ff5\u53ef\u4ee5\u7ed3\u5408\u5728\u4e00\u8d77\uff0c\u63d0\u4f9b\u4ece\u8f83\u5c0f\u5c3a\u5ea6\u5230\u8f83\u5927\u5c3a\u5ea6\u6d8c\u73b0\u7684\u666f\u89c2\u56fe\u3002\u4e2d\u95f4\u5c3a\u5ea6\u7684\u52a8\u529b\u5b66\u53ef\u4ee5\u4ece\u5c0f\u5c3a\u5ea6\u7684\u5fae\u89c2\u52a8\u529b\u5b66\u4e2d\u6d8c\u73b0\u51fa\u6765\u3002\u5fae\u89c2\u76f8\u4e92\u4f5c\u7528\u7ed9\u7cfb\u7edf\u5e26\u6765\u4e86\u7ea6\u675f\uff0c\u4f7f\u5f97\u5e76\u975e\u6240\u6709\u81ea\u7531\u5ea6\u90fd\u662f\u540c\u7b49\u53ef\u80fd\u7684\uff0c\u4e8b\u5b9e\u4e0a\uff0c\u4e00\u4e9b\u72b6\u6001\u6bd4\u53e6\u4e00\u4e9b\u72b6\u6001\u66f4\u53d7\u504f\u597d\u3002\u8fd9\u81ea\u7136\u5f62\u6210\u4e86\u4e00\u79cd\u6982\u7387\u6216\u52bf\u80fd\u666f\u89c2\u3002\u66f4\u9ad8\u6982\u7387\u7684\u72b6\u6001\u4ece\u5e95\u5c42\u5fae\u89c2\u76f8\u4e92\u4f5c\u7528\u4e2d\u6d8c\u73b0\u51fa\u6765\uff0c\u4ea7\u751f\u666f\u89c2\u4e0a\u7684\u5438\u5f15\u76c6\u5730\u3002\u4e2d\u95f4\u5c3a\u5ea6\u7684\u52a8\u529b\u5b66\u53ef\u4ee5\u7528\u6bcf\u4e2a\u72b6\u6001\u76c6\u5730\u5185\u7684\u8fd0\u52a8\u548c\u5438\u5f15\u76c6\u5730\u4e4b\u95f4\u7684\u72b6\u6001\u8f6c\u53d8\u6765\u63cf\u8ff0\u3002\u5b83\u8fd8\u53d7\u5230\u5e95\u5c42\u5feb\u901f\u5fae\u89c2\u52a8\u529b\u5b66\u7684\u5f71\u54cd\uff0c\u8fd9\u79cd\u5e95\u5c42\u5fae\u89c2\u52a8\u529b\u5b66\u9664\u4e86\u5bfc\u81f4\u6d8c\u73b0\u666f\u89c2\uff0c\u8fd8\u5bfc\u81f4\u6709\u6548\u6469\u64e6\u548c\u9a71\u52a8\u529b\u7684\u968f\u673a\u90e8\u5206[3] \uff0c\u5982\u56fe12\u6240\u793a\u3002<\/span>
<\/section>\n
     <\/span><\/section>\n
\u5728\u4e2d\u95f4\u5c3a\u5ea6\u4e0a\uff0c\u5438\u5f15\u76c6\u5730\u4e4b\u95f4\u7684\u968f\u673a\u8f6c\u53d8\u52a8\u529b\u5b66\u4e3a\u66f4\u5927\u7684\u5c3a\u5ea6\u63d0\u4f9b\u4e86\u76f8\u4e92\u4f5c\u7528\u5143\u7d20\uff0c\u8fd9\u5bfc\u81f4\u4ece\u4e2d\u95f4\u5c3a\u5ea6\u5143\u7d20\u4e4b\u95f4\u5e95\u5c42\u76f8\u4e92\u4f5c\u7528\u4e2d\u4ea7\u751f\u66f4\u5927\u5c3a\u5ea6\u4e0a\u7684\u6d8c\u73b0\u884c\u4e3a\u3002\u56e0\u6b64\uff0c\u6211\u4eec\u53ef\u4ee5\u8de8\u8d8a\u5c3a\u5ea6\u5f97\u5230\u590d\u6742\u7cfb\u7edf\u7684\u5c42\u7ea7\u7ec4\u7ec7\u3002\u4e8b\u5b9e\u4e0a\uff0c\u5bf9\u4e8e\u975e\u5e73\u8861\u7cfb\u7edf\u6765\u8bf4\uff0c\u666f\u89c2\u548c\u6d41\u90fd\u53ef\u4ee5\u4ece\u66f4\u5c0f\u5c3a\u5ea6\u5143\u7d20\u4e4b\u95f4\u7684\u5e95\u5c42\u76f8\u4e92\u4f5c\u7528\u4e2d\u6d8c\u73b0\u51fa\u6765\u3002\u4ee5\u80fd\u91cf\u666f\u89c2\u523b\u753b\u7684\u86cb\u767d\u8d28\u52a8\u529b\u5b66\u7684\u5c42\u7ea7\u7ec4\u7ec7\u5df2\u7ecf\u5728\u4e0d\u540c\u5c3a\u5ea6\u4e0a\u88ab\u5b9e\u9a8c\u8bc1\u5b9e [7-9]\u3002\u8de8\u5c3a\u5ea6\u7684\u975e\u5e73\u8861\u666f\u89c2\u548c\u6d41\u6846\u67b6\u6709\u52a9\u4e8e\u63ed\u793a\u590d\u6742\u7cfb\u7edf\u7684\u5e95\u5c42\u5c42\u7ea7\u7ec4\u7ec7\u548c\u6d8c\u73b0[3]\u3002     <\/span><\/section>\n
 <\/span><\/section>\n
<\/section>\n

\u56fe12. (a) \u6eb6\u5242-\u9ad8\u5206\u5b50\u5feb\u901f\u78b0\u649e\u7684\u793a\u610f\u56fe\uff0c\u4f5c\u4e3a\u968f\u673a\u6027\u7684\u6765\u6e90\uff0c\u4e0e\u591a\u80fd\u91cf\u9631\u666f\u89c2\u4e00\u8d77\uff0c\u5f15\u8d77\u5177\u6709\u591a\u79cd\u72b6\u6001\u7684\u5355\u4e2a\u9ad8\u5206\u5b50\u7684\u52a8\u529b\u5b66\u8df3\u8dc3\u8fc7\u7a0b\uff08\u5982\u5706\u5185\u6240\u793a\uff09\u3002(b) \u5728\u66f4\u9ad8\u5c42\u7ea7\uff0c\u8bb8\u591a\u76f8\u4e92\u4f5c\u7528\u7684\u5316\u5b66\u4e2a\u4f53\uff0c\u6bcf\u4e2a\u5177\u6709\u591a\u4e2a\u79bb\u6563\u72b6\u6001\uff0c\u4f1a\u5f62\u6210\u4ecb\u89c2\u975e\u7ebf\u6027\u53cd\u5e94\u7cfb\u7edf [3]\u3002<\/span><\/p>\n

 <\/span><\/section>\n
 <\/span><\/section>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u516d\u3001\u666f\u89c2\u548c\u6d41\u7684\u5b9e\u9a8c\u91cf\u5316<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n


<\/p>\n

\u666f\u89c2\u548c\u6d41\u7406\u8bba\u53ef\u4ee5\u901a\u8fc7\u5b9e\u9a8c\u8fdb\u884c\u68c0\u9a8c\u548c\u91cf\u5316\u3002\u65e9\u671f\u7531 Hans \u9886\u5bfc\u7684\u914d\u4f53\u4e0e\u808c\u7ea2\u86cb\u767d\u548c\u8840\u7ea2\u86cb\u767d\u7ed3\u5408\u7684\u5f00\u62d3\u6027\u5de5\u4f5c\uff0c\u63ed\u793a\u4e86\u5206\u5e03\u5f0f\u52a8\u529b\u5b66\u548c\u76f8\u5173\u7684\u5e95\u5c42\u590d\u6742\u80fd\u91cf\u666f\u89c2\u7ed3\u6784 [7-10]\u3002     <\/span>
<\/section>\n

<\/section>\n
\u5728\u66f4\u5927\u89c4\u6a21\uff0c\u6280\u672f\u7684\u5feb\u901f\u53d1\u5c55\u4f7f\u5f97\u5b9e\u65f6\u89c2\u5bdf\u57fa\u56e0\u8868\u8fbe\u52a8\u529b\u5b66<\/strong>\u6210\u4e3a\u53ef\u80fd\u3002\u4f8b\u5982\uff0c\u53ef\u4ee5\u5c06\u7eff\u8272\u8367\u5149\u86cb\u767d<\/span>\uff08GFP\uff09<\/span>\u5206\u5b50\u6574\u5408\u5e76\u9644\u7740\u5728\u57fa\u56e0\u8868\u8fbe\u4ea7\u7269\u86cb\u767d\u4e0a\uff0c\u8fd9\u6837\u76f8\u5173\u7684\u8367\u5149\u5f3a\u5ea6\u5c31\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u57fa\u56e0\u8868\u8fbe\u6c34\u5e73\u6216\u86cb\u767d\u8d28\u6d53\u5ea6\u3002\u5149\u5f3a\u968f\u65f6\u95f4\u968f\u673a\u6ce2\u52a8\uff0c\u5355\u4e2a\u5206\u5b50\u7684\u8367\u5149\u5f3a\u5ea6\u5728\u65f6\u95f4\u4e0a\u662f\u4e0d\u786e\u5b9a\u3001\u4e0d\u53ef\u9884\u6d4b\u7684\uff0c\u4f46\u8367\u5149\u5f3a\u5ea6\u7684\u7edf\u8ba1\u6a21\u5f0f\u53ef\u4ee5\u662f\u89c4\u5219\u7684\uff0c\u5e76\u7528\u4e8e\u8868\u5f81\u56fe13\u5de6\u56fe\u4e2d\u663e\u793a\u7684\u52a8\u529b\u5b66\u3002\u56e0\u6b64\uff0c\u53ef\u4ee5\u6536\u96c6\u5149\u5f3a\u968f\u65f6\u95f4\u53d8\u5316\u7684\u7edf\u8ba1\u6570\u636e\uff0c\u5e76\u83b7\u5f97\u76f8\u5173\u5206\u5e03\u3002\u8fd9\u4e2a\u5206\u5e03\u7684\u8d1f\u5bf9\u6570\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u5e95\u5c42\u666f\u89c2 [157,158]\u3002<\/span><\/section>\n
 <\/span><\/section>\n

\n
<\/section>\n<\/h1>\n

\u56fe13. \u5de6\uff1a\u76f4\u65b9\u56fe\u7ed9\u51fa\u4e86\u4ece\u5b9e\u65f6\u5b9e\u9a8c\u4e2d\u6536\u96c6\u7684\u81ea\u6291\u5236\u57fa\u56e0\u73af\u8def\u7684163\u4e2a\u5355\u7ec6\u80de\u8367\u5149\u8f68\u8ff9\u7684\u5f3a\u5ea6\u5206\u5e03\u3002\u7ea2\u8272\u66f2\u7ebf\u662f HMM \u7684\u62df\u5408\u5f3a\u5ea6\u5206\u5e03 [158]\u3002\u53f3\uff1a\u52bf\u80fd\u666f\u89c2\u662f\u901a\u8fc7\u5b9e\u9a8c\u6d4b\u91cf\u7684\u03bb \u566c\u83cc\u4f53\u7cfb\u7edf\u4e24\u79cd\u57fa\u56e0\u8868\u8fbe\u6570\u503c\u7684 2D \u76f4\u65b9\u56fe\u8ba1\u7b97\u6240\u5f97\u3002\u56fe\u4e2dH\u8868\u793a CI \u548c Cro \u7684\u9ad8\u8868\u8fbe\uff0cL \u8868\u793a\u4f4e\u8868\u8fbe\uff0c\u7ec4\u5408\u8d77\u6765\u5171\u56db\u79cd\u8868\u8fbe\u72b6\u6001 [157]\u3002<\/span><\/p>\n

 <\/span><\/section>\n
\u5bf9\u4e8e\u7ec6\u83cc\u4e2d\u7684\u81ea\u6211\u6291\u5236\u57fa\u56e0<\/strong>\uff0c\u5982\u5927\u80a0\u6746\u83cc\u4e2d\u7684 TetR\uff0c\u4eba\u4eec\u671f\u671b\u89c2\u5bdf\u5230\u4ee5\u6291\u5236\u57fa\u56e0\u8868\u8fbe\u4e3a\u4e2d\u5fc3\u7684\u5355\u5cf0\u5206\u5e03\u3002\u901a\u8fc7\u5f15\u5165\u8bf1\u5bfc\u5206\u5b50\u7834\u574f\u81ea\u6211\u6291\u5236\u5242\u4e0e\u57fa\u56e0\u7684\u7ed3\u5408\u8fc7\u7a0b\uff0c\u53ef\u4ee5\u6709\u6548\u51cf\u7f13\u57fa\u56e0\u8c03\u63a7\u8fc7\u7a0b\u3002\u8fd9\u6837\u5f53\u81ea\u6211\u6291\u5236\u5242\u4e0d\u4e0e\u57fa\u56e0\u7ed3\u5408\u65f6\uff0c\u57fa\u56e0\u5c31\u6709\u53ef\u80fd\u88ab\u6fc0\u6d3b\u3002\u8367\u5149\u5f3a\u5ea6\u7684\u5b9e\u9a8c\u5b9e\u65f6\u89c2\u6d4b\u8868\u660e\uff0c\u5728\u7279\u5b9a\u8bf1\u5bfc\u5242\u6d53\u5ea6\u4e0b\u51fa\u73b0\u4e86\u53cc\u5cf0\u5206\u5e03\u3002\u8fd9\u91cf\u5316\u4e86\u5177\u6709\u4e24\u4e2a\u5438\u5f15\u76c6\u5730\u7684\u5e95\u5c42\u666f\u89c2 [158]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u53e6\u4e00\u4e2a\u4f8b\u5b50\u662f\u5927\u80a0\u6746\u83cc\u4e2d\u7684 \u03bb \u566c\u83cc\u4f53\u7cfb\u7edf<\/strong> [159]\u3002\u03bb \u566c\u83cc\u4f53\u88ab\u8ba4\u4e3a\u6709\u4e24\u79cd\u547d\u8fd0\uff0c\u7531\u4e24\u79cd\u76f8\u4e92\u6291\u5236\u7684\u57fa\u56e0\u63a7\u5236\u3002\u5229\u7528\u65b0\u8fd1\u53d1\u5c55\u8d77\u6765\u7684\u5171\u5b9a\u4f4d<\/span>\uff08co-localization\uff09<\/span>\u6280\u672f\uff0c\u53ef\u4ee5\u4f7f\u7528\u76f8\u540c\u989c\u8272\u7684\u8367\u5149\u5206\u5b50\u6807\u8bb0\u4e24\u79cd\u57fa\u56e0\u5728\u4e0d\u540c\u4f4d\u7f6e\u7684\u8868\u8fbe\uff0c\u66f4\u771f\u5b9e\u5730\u8fd8\u539f\u57fa\u56e0\u7684\u5b9e\u65f6\u8868\u8fbe\u60c5\u51b5\u3002\u8fd9\u4f7f\u5f97\u6211\u4eec\u53ef\u4ee5\u8ffd\u8e2a \u03bb \u566c\u83cc\u4f53\u4e2d CI \u548c Cro \u4e24\u79cd\u8f6c\u5f55\u56e0\u5b50\u5728\u6e29\u5ea6\u654f\u611f\u7a81\u53d8\u4e0b\u7684\u5408\u6210\u73af\u8def\u52a8\u529b\u5b66\u3002\u4ece\u56fe12\u53f3\u56fe\u4e0a\u663e\u793a\u7684\u5b9e\u65f6\u8f68\u8ff9\u7684\u7edf\u8ba1\u5b66\u4e2d\u53ef\u4ee5\u89c2\u5bdf\u5230\u56db\u4e2a\u5cf0\u503c\uff0c\u4e5f\u5c31\u662f\u51fa\u73b0\u4e86\u5177\u6709\u56db\u4e2a\u76c6\u5730\u7684\u666f\u89c2\u3002\u66f4\u8fdb\u4e00\u6b65\uff0c\u8fd9\u4e9b\u72b6\u6001\u4e4b\u95f4\u7684\u8f6c\u53d8\u7387\u53ef\u4ee5\u901a\u8fc7\u5bf9\u5b9e\u65f6\u6570\u636e\u7684\u9690\u9a6c\u5c14\u53ef\u592b\u94fe\u5206\u6790\u8fdb\u884c\u91cf\u5316\u3002\u6b64\u5916\uff0c\u4eba\u4eec\u53d1\u73b0\uff0c\u4ece CI \u5230 Cro \u6216\u53cd\u4e4b\u7684\u4e3b\u8981\u8f6c\u53d8\u8def\u5f84\u5e76\u975e\u76f4\u63a5\u7684\u90a3\u6761\uff0c\u800c\u662f\u901a\u8fc7 CI \u548c Cro \u7684\u9ad8\u8868\u8fbe\u72b6\u6001\u5b9e\u73b0\u7684 [157]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u5982\u524d\u6240\u8ff0\uff0c\u53ef\u4ee5\u5229\u7528\u56fe14\u6240\u793a\u7684\u5b9e\u65f6\u8f68\u8ff9\u7684\u7edf\u8ba1\u6570\u636e\u901a\u8fc7\u5b9e\u9a8c\u6765\u91cf\u5316\u666f\u89c2\uff0c\u4e5f\u53ef\u4ee5\u901a\u8fc7\u5b9e\u9a8c\u6765\u91cf\u5316\u6d41\u3002\u901a\u8fc7\u7814\u7a76\u8fa3\u6839\u8fc7\u6c27\u5316\u7269\u9176<\/span>\uff08HRP\uff09<\/span>\u5728\u4e8c\u6c22\u7f57\u4e39\u660e 123<\/span>\uff08DHR\uff09<\/span>\u548c\u8fc7\u6c27\u5316\u6c22<\/span>\uff08H2<\/sub><\/span>O2<\/sub><\/span>\uff09<\/span>\u4f5c\u7528\u4e0b\u7684\u5355\u5206\u5b50\u9176\u52a8\u529b\u5b66<\/strong>\uff0c\u5b9e\u9a8c\u53d1\u73b0\u4e0e\u4f20\u7edf\u7684 Michaelis-Menten \u52a8\u529b\u5b66\u5b58\u5728\u504f\u5dee\u3002\u8be6\u7ec6\u5206\u6790\u8868\u660e\uff0c\u975e\u5e73\u8861\u6d41\u662f\u8fd9\u79cd\u975e Michaelis-Menten \u884c\u4e3a\u7684\u6765\u6e90\uff0c\u53ef\u4ee5\u901a\u8fc7\u8367\u5149\u76f8\u5173\u5149\u8c31\u4ece\u5355\u4e00\u9176\u52a8\u529b\u5b66\u7684\u5b9e\u65f6\u8f68\u8ff9\u6765\u91cf\u5316\u3002\u5bf9\u4e8e\u8fd9\u79cd\u975e Michaelis-Menten \u884c\u4e3a\uff0c\u53ef\u4ee5\u8fdb\u4e00\u6b65\u91cf\u5316\u5316\u5b66\u52bf\u548c\u71b5\u4ea7\u751f\u4f5c\u4e3a\u975e\u5e73\u8861\u70ed\u529b\u5b66\u9a71\u52a8\u529b\u3002\u901a\u8fc7\u7b49\u6e29\u6ef4\u5b9a\u91cf\u70ed\u6cd5\uff0c\u53ef\u4ee5\u786e\u5b9a\u9176\u53cd\u5e94\u5438\u6536\u7684\u70ed\u91cf\u662f\u975e\u5e73\u8861\u6d41\u548c\u975e\u5e73\u8861\u70ed\u529b\u5b66\u7684\u6765\u6e90\u3002\u8fd9\u53ef\u4ee5\u63d0\u4f9b\u4e00\u79cd\u901a\u7528\u65b9\u6cd5\u6765\u91cf\u5316\u975e\u5e73\u8861\u7cfb\u7edf\u7684\u52a8\u529b\u5b66\u548c\u70ed\u529b\u5b66\u9a71\u52a8\u529b[5,160]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
    <\/span><\/section>\n

\u56fe14. HRP \u6700\u7b80\u5355\u7684\u52a8\u529b\u5b66\u7ed3\u6784\uff0c\u5177\u67092\u4e2a\u672a\u7ed3\u5408\u9176\u72b6\u6001\uff0c\u548c\u975e\u96f6\u5185\u90e8\u73af\u8def\u6d41 J\u3002E1<\/sub><\/span> \u548c E2<\/sub><\/span> \u662f\u81ea\u7531 HRP \u7684\u4e24\u79cd\u4e0d\u540c\u6784\u8c61\uff0cES \u662f HRP \u7684\u5e95\u7269\u7ed3\u5408\u6001\u3002[160]<\/span><\/p>\n

 <\/span><\/section>\n
 <\/span><\/section>\n

\n
\n
\n
\n
\n

<\/section>\n

<\/section>\n
\n
<\/svg><\/section>\n<\/section>\n<\/section>\n
\n

\u4e03\u3001\u5c55\u671b<\/span><\/strong><\/strong><\/p>\n<\/section>\n

\n

<\/section>\n

<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/h3>\n


<\/p>\n

\u8fd9\u7bc7\u7efc\u8ff0\u8ba8\u8bba\u4e86\u666f\u89c2\u7684\u6982\u5ff5\u4ee5\u53ca\u7406\u89e3\u590d\u6742\u7cfb\u7edf\u6d8c\u73b0\u884c\u4e3a\u7684\u6d41\u7406\u8bba\u3002\u603b\u4f53\u800c\u8a00\uff0c\u666f\u89c2\u548c\u6d41\u662f\u5e73\u8861\u548c\u975e\u5e73\u8861\u52a8\u529b\u7cfb\u7edf\u7684\u9a71\u52a8\u529b\uff0c\u5e76\u4ea7\u751f\u4e86\u5e73\u8861\u6001\u548c\u975e\u5e73\u8861\u6001\u70ed\u529b\u5b66\u3002<\/span>
<\/section>\n

<\/section>\n
\u975e\u5e73\u8861\u7cfb\u7edf\u7684\u666f\u89c2\u548c\u6d41\u7406\u8bba\u4e3a\u5e73\u8861\u7cfb\u7edf\u63d0\u4f9b\u4e86\u4e0e\u4f20\u7edf\u89c2\u70b9\u4e0d\u540c\u7684\u89c6\u89d2\u3002\u4f20\u7edf\u7684\u903b\u8f91\u662f\uff0c\u590d\u6742\u7cfb\u7edf\u7684\u6d8c\u73b0\u884c\u4e3a\u6765\u81ea\u5e95\u5c42\u76f8\u4e92\u4f5c\u7528\u5f62\u6210\u7684\u80fd\u91cf\u666f\u89c2\uff0c\u8fd9\u662f\u5148\u9a8c\u5df2\u77e5\u7684\u3002\u8fd9\u5bf9\u4e8e\u5e73\u8861\u7cfb\u7edf\u6765\u8bf4\u5f53\u7136\u662f\u6b63\u786e\u7684\uff0c\u7136\u800c\uff0c\u5bf9\u4e8e\u975e\u5e73\u8861\u7cfb\u7edf\uff0c\u4f20\u7edf\u7684\u63cf\u8ff0\u5931\u8d25\u4e86\uff0c\u56e0\u4e3a\u5f80\u5f80\u6ca1\u6709\u4e00\u4e2a\u5148\u9a8c\u5df2\u77e5\u7684\u80fd\u91cf\u666f\u89c2\u8ba9\u52a8\u529b\u5b66\u8ddf\u968f\u3002\u4e8b\u5b9e\u4e0a\uff0c\u52a8\u529b\u5b66\u4e0d\u4ec5\u7531\u666f\u89c2\u51b3\u5b9a\uff0c\u4e5f\u7531\u975e\u5e73\u8861\u6d41\u51b3\u5b9a\uff0c\u800c\u666f\u89c2\u548c\u6d41\u672c\u8eab\u662f\u52a8\u529b\u5b66\u8fc7\u7a0b\u7684\u7ed3\u679c<\/strong>\u3002\u8fd9\u8868\u660e\u52a8\u529b\u5b66\u7684\u5168\u5c40\u9a71\u52a8\u529b\u53ef\u80fd\u5e76\u4e0d\u603b\u662f\u7531\u4f20\u7edf\u7684\u76f8\u4e92\u4f5c\u7528\u80fd\u91cf\u51b3\u5b9a\uff0c\u56e0\u4e3a\u5b83\u4eec\u4e0d\u4e00\u5b9a\u662f\u5148\u9a8c\u5df2\u77e5\u7684\u3002\u7136\u800c\uff0c\u6982\u7387\u666f\u89c2\u548c\u6982\u7387\u6d41\u4ecd\u7136\u770b\u8d77\u6765\u53ef\u4ee5\u4ece\u5168\u5c40\u4e0a\u786e\u5b9a\u52a8\u529b\u5b66\u3002     <\/span><\/section>\n

<\/section>\n
\u7531\u4e8e\u666f\u89c2\u548c\u6d41\u53ef\u4ee5\u533a\u5206\u72b6\u6001\u7684\u6743\u91cd\u548c\u72b6\u6001\u4e4b\u95f4\u7684\u6d41\uff0c\u6211\u4eec\u53ef\u4ee5\u5173\u6ce8\u51fa\u73b0\u6982\u7387\u9ad8\u7684\u72b6\u6001\u4ee5\u53ca\u5b83\u4eec\u4e4b\u95f4\u7684\u76f8\u5173\u6027\u3002\u901a\u8fc7\u4e13\u6ce8\u4e8e\u8fd9\u4e9b\u76f8\u5bf9\u201c\u7a33\u5b9a\u201d<\/span>\uff08\u9ad8\u6743\u91cd\uff09<\/span>\u6216\u201c\u7f13\u6162\u201d \u72b6\u6001\u53d8\u91cf\u7684\u52a8\u529b\u5b66\uff0c\u540c\u65f6\u5e73\u5747\u6216\u7c97\u7c92\u5316\u201c\u77ac\u6001\u201d\u6216\u201c\u5feb\u901f\u201d\u72b6\u6001\u53d8\u91cf\uff0c\u53ef\u4ee5\u6709\u6548\u964d\u4f4e\u7cfb\u7edf\u7684\u7ef4\u5ea6 [5,6,74,156]\u3002\u5269\u4f59\u7684\u5177\u6709\u8f83\u4f4e\u7ef4\u5ea6\u7684\u201c\u7f13\u6162\u201d\u81ea\u7531\u5ea6\u5b58\u5728\u4e8e\u4ece\u5fae\u89c2\u5c3a\u5ea6\u7684\u81ea\u7531\u5ea6\u6d8c\u73b0\u51fa\u7684\u65b0\u7684\u4ecb\u89c2\u5c3a\u5ea6[3,5,6]\u3002\u56e0\u6b64\uff0c\u4ecb\u89c2\u5c3a\u5ea6\u7684\u52a8\u529b\u5b66\u89c4\u5f8b\u7531\u72b6\u6001\u7a7a\u95f4\u4e2d\u8f83\u4f4e\u7ef4\u5ea6\u7684\u5fae\u89c2\u81ea\u7531\u5ea6\u7684\u5e95\u5c42\u52a8\u529b\u5b66\u4e2d\u6d8c\u73b0\u51fa\u7684\u72b6\u6001\u4e4b\u95f4\u7684\u5173\u8054\u548c\u8f6c\u53d8\u51b3\u5b9a\u3002\u4e8b\u5b9e\u4e0a\uff0c\u4ecb\u89c2\u5c3a\u5ea6\u7684\u968f\u673a\u52a8\u529b\u5b66\u53c8\u662f\u7531\u72b6\u6001\u7a7a\u95f4\u4e2d\u8f83\u4f4e\u7ef4\u5ea6\u7684\u201c\u7f13\u6162\u201d\u72b6\u6001\u4e4b\u95f4\u7684\u5173\u8054\u4e2d\u6d8c\u73b0\u51fa\u7684\u666f\u89c2\u548c\u6d41\u51b3\u5b9a\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u51b3\u5b9a\u52a8\u529b\u5b66\u7684\u666f\u89c2\u548c\u6d41\u4e5f\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u5fae\u89c2\u548c\u4ecb\u89c2\u5c3a\u5ea6\u4e0a\u7684\u975e\u5e73\u8861\u70ed\u529b\u5b66\u548c\u7edf\u8ba1\u529b\u5b66\u3002\u53ef\u4ee5\u9884\u8ba1\uff0c\u666f\u89c2\u548c\u6d41\u65b9\u9762\u7684\u4ecb\u89c2\u5c3a\u5ea6\u52a8\u529b\u5b66\u7684\u7ed3\u679c\uff0c\u53ef\u4ee5\u8fdb\u4e00\u6b65\u533a\u5206\u4ecb\u89c2\u5c3a\u5ea6\u4e0a\u8f83\u9ad8\u6743\u91cd\u7684\u72b6\u6001\u53ca\u5176\u4e4b\u95f4\u7684\u6d41\u3002\u56e0\u6b64\uff0c\u8fd9\u4e3a\u5efa\u7acb\u5b8f\u89c2\u5c3a\u5ea6\u4e0b\u7684\u52a8\u529b\u5b66\u53ca\u5176\u76f8\u5173\u89c4\u5f8b\uff0c\u4ee5\u53ca\u66f4\u9ad8\u5c3a\u5ea6<\/span>\uff08\u6bd4\u5982\u5b8f\u89c2\u5c3a\u5ea6\uff09<\/span>\u7684\u76f8\u5e94\u975e\u5e73\u8861\u6001\u70ed\u529b\u5b66<\/span>\uff08\u6211\u4eec\u8ba4\u4e3a\u8fd9\u518d\u6b21\u7531\u666f\u89c2\u548c\u6d41\u51b3\u5b9a\uff09<\/span>\u63d0\u4f9b\u4e86\u57fa\u7840\u3002\u8fd9\u4e2a\u8fc7\u7a0b\u53ef\u4ee5\u7ee7\u7eed\u4ea7\u751f\u4e0d\u540c\u5c3a\u5ea6\u6216\u7ec4\u7ec7\u5c42\u7ea7\u7684\u7269\u8d28\u72b6\u6001\u548c\u76f8\u5173\u7684\u52a8\u529b\u5b66\u5b9a\u5f8b\uff0c\u4ee5\u53ca\u76f8\u5e94\u7684\u81ea\u4e0b\u800c\u4e0a\u7684\u975e\u5e73\u8861\u70ed\u529b\u5b66\u3002     <\/span><\/section>\n
   <\/span><\/section>\n
\u91cd\u8981\u7684\u662f\uff0c\u666f\u89c2\u548c\u6d41\u7684\u4fe1\u606f\u53ef\u4ee5\u4ece\u5b9e\u65f6\u8ffd\u8e2a\u7684\u5b9e\u9a8c\u89c2\u6d4b\u7684\u7edf\u8ba1\u5b66\u548c\u76f8\u5173\u6027\u4e2d\u83b7\u5f97\u3002\u7531\u4e8e\u6982\u7387\u666f\u89c2\u548c\u6982\u7387\u6d41\u53ef\u4ee5\u9a71\u52a8\u5168\u5c40\u52a8\u529b\u5b66\uff0c\u8fd9\u610f\u5473\u7740\u51b3\u5b9a\u52a8\u529b\u5b66\u7684\u57fa\u672c\u529b\u5b9a\u5f8b<\/span>\uff08fundamental force law\uff09<\/span>\u53ef\u4ee5\u4ece\u89c2\u6d4b<\/span>\uff08\u6570\u636e\uff09<\/span>\u7684\u7edf\u8ba1\u5b66\u548c\u76f8\u5173\u6027\u4e2d\u4ea7\u751f\u3002\u4e0d\u50cf\u725b\u987f\u8fd0\u52a8\u5b9a\u5f8b\u4e00\u6837\u4ece\u6700\u5e95\u5c42\u5efa\u7acb\u57fa\u672c\u529b\u5b9a\u5f8b\uff0c\u6211\u4eec\u73b0\u5728\u53ef\u4ee5\u770b\u5230\uff0c\u52a8\u529b\u5b66\u7684\u57fa\u672c\u529b\u5b9a\u5f8b\u53ef\u4ee5\u901a\u8fc7\u6570\u5b57\u8ba1\u6570\u548c\u89c2\u6d4b\u6570\u636e\u4e2d\u6570\u5b57\u4e4b\u95f4\u7684\u7edf\u8ba1\u5173\u8054\uff0c\u4ee5\u7edf\u8ba1\u65b9\u5f0f\u81ea\u4e0a\u800c\u4e0b\u6d8c\u73b0\u51fa\u6765<\/strong>\u3002\u5c3d\u7ba1\u5e73\u8861\u6001\u70ed\u529b\u5b66\u548c\u7edf\u8ba1\u529b\u5b66\u901a\u5e38\u7531\u81ea\u4e0b\u800c\u4e0a<\/strong>\u7684\u5e95\u5c42\u76f8\u4e92\u4f5c\u7528\u80fd\u51b3\u5b9a\uff0c\u4e00\u822c\u7684\u5e73\u8861\u6001\u548c\u975e\u5e73\u8861\u6001\u70ed\u529b\u5b66\u4ee5\u53ca\u76f8\u5173\u7684\u7edf\u8ba1\u529b\u5b66\uff0c\u53ef\u4ee5\u901a\u8fc7\u4ee5\u81ea\u4e0a\u800c\u4e0b<\/strong>\u65b9\u5f0f\u4ece\u52a8\u529b\u5b66\u4e2d\u6d8c\u73b0\u7684\u6982\u7387\u666f\u89c2\u548c\u6982\u7387\u6d41\u5f97\u5230\u53d1\u5c55\u3002\u8fd9\u518d\u6b21\u8868\u660e\uff0c\u57fa\u672c\u529b\u5b9a\u5f8b\u548c\u76f8\u5e94\u7684\u6d8c\u73b0\u70ed\u529b\u5b66\u4ee5\u53ca\u76f8\u5173\u7684\u7edf\u8ba1\u529b\u5b66\uff0c\u90fd\u53ef\u80fd\u6765\u81ea\u6982\u7387\u666f\u89c2\u548c\u6982\u7387\u6d41[6]\u3002<\/span><\/section>\n
 <\/span><\/section>\n
\u8fd9\u5728\u67d0\u79cd\u610f\u4e49\u4e0a\u662f\u76f4\u89c2\u7684\uff0c\u56e0\u4e3a\u6211\u4eec\u53ef\u4ee5\u4f9d\u8d56\u7684\u6700\u57fa\u672c\u4e1c\u897f\u6bd5\u7adf\u662f\u6570\u5b57\u548c\u51e0\u4f55\u3002\u6570\u5b57<\/span>\uff08\u9891\u7387\/\u6982\u7387\uff09<\/span>\u7684\u7edf\u8ba1\u548c\u8868\u793a\u5b83\u4eec\u4e4b\u95f4\u5173\u8054\u7684\u3001\u5177\u6709\u5e95\u5c42\u51e0\u4f55\/\u62d3\u6251\u7ed3\u6784\u7684\u6d41<\/span>\uff08\u901a\u91cf\uff09<\/span>[5,6,203]\uff0c\u53ef\u80fd\u662f\u4e0d\u540c\u5c3a\u5ea6\u7684\u57fa\u672c\u89c4\u5f8b\u548c\u6d8c\u73b0\u89c4\u5f8b\u7684\u57fa\u672c\u6784\u4ef6[6]\u3002\u56e0\u6b64\uff0c\u6839\u636e\u8fd9\u4e2a\u903b\u8f91\uff0c\u5b9e\u9645\u4e2d\u666f\u89c2\u548c\u6d41\u53ef\u4ee5\u4ece\u89c2\u6d4b\u6570\u636e\u7684\u7edf\u8ba1\u548c\u76f8\u5173\u6027\u4e2d\u83b7\u5f97\u3002\u8fd9\u5c31\u7ed9\u51fa\u4e86\u89c2\u6d4b\u5c3a\u5ea6\u4e0a\u7684\u52a8\u529b\u5b66\u5b9a\u5f8b\u548c\u76f8\u5e94\u7684\u70ed\u529b\u5b66\u3002     <\/span><\/section>\n
 <\/span><\/section>\n
\u53e6\u4e00\u65b9\u9762\uff0c\u901a\u8fc7\u9690\u9a6c\u5c14\u53ef\u592b\u94fe\u5206\u6790\uff0c\u91cd\u8981\u72b6\u6001\u53ca\u5176\u76f8\u5173\u6027\u53ef\u4ee5\u4ece\u5b9e\u65f6\u8ffd\u8e2a\u4e2d\u8fdb\u4e00\u6b65\u6d8c\u73b0\uff0c\u5bfc\u81f4\u7ef4\u6570\u663e\u8457\u964d\u4f4e\u3002\u5b83\u53ef\u4ee5\u4ea7\u751f\u7531\u72b6\u6001\u7684\u7edf\u8ba1\u53ca\u5176\u76f8\u5173\u6027\u4e2d\u6d8c\u73b0\u7684\u666f\u89c2\u548c\u6d41\u6240\u652f\u914d\u7684\u529b\u5b9a\u5f8b\uff0c\u4ee5\u53ca\u8fd9\u4e2a\u65b0\u7684\u6d8c\u73b0\u5c3a\u5ea6\u4e0a\u7684\u76f8\u5173\u70ed\u529b\u5b66\u3002\u8fd9\u4ece\u5173\u7cfb\u54f2\u5b66\u4e0a\u63d0\u4f9b\u4e86\u5b9e\u4f53\u548c\u5173\u7cfb\u51b3\u5b9a\u4e16\u754c\u7684\u5b9a\u91cf\u57fa\u7840\u548c\u5b9e\u73b0[6,194,195]\u3002\u540c\u6837\u91cd\u8981\u7684\u662f\uff0c\u9700\u8981\u8ba4\u8bc6\u5230\u9759\u529b\u5b66\u4e0d\u662f\u4e16\u754c\u7684\u56fa\u6709\u672c\u8d28\uff0c\u52a8\u529b\u5b66\u6216\u968f\u65f6\u95f4\u7684\u6f14\u5316\u624d\u662f\u3002\u56e0\u6b64\uff0c\u57fa\u4e8e<\/span>\uff08\u5b9e\u9a8c\u89c2\u5bdf\uff09<\/span>\u7684\u6570\u5b57\/\u6d41\u7684\u7edf\u8ba1\u53ca\u4e4b\u95f4\u76f8\u5173\u6027\u7684\u57fa\u672c\u6784\u5efa\u5757\uff0c\u4f1a\u5bfc\u81f4\u5e95\u5c42\u548c\u6d8c\u73b0\u5c42\u9762\u7684\u52a8\u6001\u6f14\u5316\u5b9a\u5f8b[6]\uff0c\u7ed9\u51fa\u8fc7\u7a0b\u54f2\u5b66\u7684\u5b9a\u91cf\u57fa\u7840 [194]\u3002<\/span><\/section>\n

<\/section>\n
\u51b3\u5b9a\u52a8\u529b\u5b66\u7684\u6982\u7387\u548c\u6982\u7387\u6d41\u4e5f\u53ef\u4ee5\u7528\u6765\u91cf\u5316\u71b5\u548c\u71b5\u6d41\uff0c\u4ece\u800c\u7ed9\u51fa\u76f8\u5e94\u7684\u70ed\u529b\u5b66[5,6]\u3002\u6211\u4eec\u53ef\u4ee5\u53cd\u8fc7\u6765\u95ee\u8fd9\u6837\u4e00\u4e2a\u95ee\u9898\uff1a\u5982\u679c\u5728\u5f53\u524d\u5c3a\u5ea6\u4e0a\u628a\u70ed\u529b\u5b66\u770b\u505a\u662f\u201c\u57fa\u672c\u7684\u201d\uff0c\u90a3\u4e48\u52a8\u529b\u5b66\u5b9a\u5f8b\u662f\u5426\u53ef\u4ee5\u4ece\u70ed\u529b\u5b66\u4e2d\u4ea7\u751f\u6216\u201c\u63a8\u5bfc\u201d\u51fa\u6765\u3002\u4ece\u8fd9\u4e2a\u89d2\u5ea6\u6765\u770b\uff0c\u70ed\u529b\u5b66\u7684\u72b6\u6001\u65b9\u7a0b\u53ef\u4ee5\u770b\u4f5c\u662f\u652f\u914d\u52a8\u529b\u5b66\u7684\u5b9a\u5f8b<\/strong>\u3002\u4e00\u4e2a\u4f8b\u5b50\u6765\u81ea\u81a8\u80c0\u7684\u5b87\u5b99\uff0c\u5b87\u5b99\u7684\u6f14\u5316\u52a8\u529b\u5b66\u53ef\u4ee5\u770b\u4f5c\u662f\u5e95\u5c42\u70ed\u529b\u5b66\u7684\u72b6\u6001\u65b9\u7a0b[196]\u3002\u66f4\u4e00\u822c\u5730\uff0c\u65f6\u7a7a\u52a8\u529b\u5b66\u7684\u7231\u56e0\u65af\u5766\u65b9\u7a0b\u53ef\u4ee5\u770b\u4f5c\u662f\u72b6\u6001\u65b9\u7a0b\uff0c\u5e76\u4ece\u70ed\u529b\u5b66\u63a8\u5bfc\u800c\u6765[197] \u3002\u56e0\u6b64\uff0c\u5f15\u529b\u53ef\u80fd\u5177\u6709\u71b5\u6216\u70ed\u529b\u5b66\u8d77\u6e90[198]\u3002\u4ece\u8fd9\u4e2a\u89d2\u5ea6\u6765\u770b\uff0c\u5404\u79cd\u5f62\u5f0f\u7684\u52a8\u529b\u5b66\uff0c\u5982\u8fd0\u52a8\u65b9\u7a0b[196,197]\u548c\u65f6\u95f4\u4f9d\u8d56\u7684\u6c49\u5bc6\u5c14\u987f-\u96c5\u53ef\u6bd4\u65b9\u7a0b[5,6,204]\uff0c\u53ef\u4ee5\u770b\u4f5c\u662f\u4ece\u57fa\u4e8e\u666f\u89c2\u548c\u6d41\u7684\u70ed\u529b\u5b66<\/span>\uff08\u7b2c\u4e00\u5b9a\u5f8b\u548c\u7b2c\u4e8c\u5b9a\u5f8b\uff09<\/span>\u4e2d\u6d8c\u73b0\u51fa\u7684\u6f14\u5316\u7684<\/span>\uff08\u72b6\u6001\uff09<\/span>\u65b9\u7a0b\uff0c\u65e0\u8bba\u662f\u5e73\u8861\u6001\u8fd8\u662f\u975e\u5e73\u8861\u6001\u3002     <\/span><\/section>\n

<\/span><\/section>\n
\u53e6\u4e00\u65b9\u9762\uff0c\u6982\u7387\u548c\u6982\u7387\u6d41\u53ef\u4ee5\u7528\u6765\u8868\u793a\u4fe1\u606f\u548c\u4fe1\u606f\u6d41[199-201]\u3002\u8fd9\u8868\u660e\u4fe1\u606f\u548c\u4fe1\u606f\u6d41\u4e5f\u53ef\u4ee5\u4f5c\u4e3a\u57fa\u672c\u5b9a\u5f8b\u7684\u6784\u4ef6\u3002\u4f9d\u7167\u60e0\u52d2\u6700\u521d\u63d0\u51fa\u201c\u4e07\u7269\u6e90\u4e8e\u6bd4\u7279\u201d<\/span>\uff08it from bit\uff09<\/span>\u7684\u7cbe\u795e\uff0c\u4e00\u4e9b\u7ebf\u7d22\u5df2\u7ecf\u8868\u660e\u4fe1\u606f\u548c\u65f6\u7a7a\u4e4b\u95f4\u5b58\u5728\u8054\u7cfb\u3002\u4e16\u754c\u7684\u672c\u6e90\u6216\u8bb8\u7ec8\u7a76\u662f\u4fe1\u606f\u6216\u71b5\uff1a\u6570\u5b57\u53ca\u5176\u76f8\u5173\u6027\u7684\u7edf\u8ba1\u4f5c\u4e3a\u5b58\u5728\u7684\u57fa\u672c\u5b9e\u4f53<\/strong>\u3002\u56e0\u6b64\uff0c\u5bf9\u4e8e\u751f\u7269\u4fe1\u606f\u5904\u7406\uff0c\u4f8b\u5982\u7ec6\u80de\u548c\u8111\u529f\u80fd\u800c\u8a00\uff0c\u4fe1\u606f\u7684\u89c2\u70b9\u662f\u975e\u5e38\u91cd\u8981\u7684[205]\uff0c\u9700\u8981\u66f4\u591a\u5173\u6ce8\u548c\u7814\u7a76\u3002<\/span><\/section>\n

<\/section>\n
\u672a\u6765\uff0c\u666f\u89c2\u548c\u6d41\u7684\u6982\u5ff5\u548c\u5e94\u7528\u53ef\u4ee5\u63a8\u5e7f\u5230\u7a7a\u95f4\u65f6\u95f4\u52a8\u529b\u5b66[175,176,206-208] \uff0c\u63ed\u793a\u590d\u6742\u751f\u7269\u7cfb\u7edf\u7684\u6d8c\u73b0\u884c\u4e3a\u5982\u4f55\u5728\u7a7a\u95f4\u548c\u65f6\u95f4\u4e2d\u4ea7\u751f\u3002\u53e6\u4e00\u4e2a\u91cd\u8981\u65b9\u9762\u662f\u5728\u5206\u5b50\u6c34\u5e73\u63cf\u8ff0\u548c\u7ec6\u80de\u63cf\u8ff0\uff0c\u4ee5\u53ca\u7ec6\u80de\u6c34\u5e73\u63cf\u8ff0\u548c\u751f\u7269\u4f53\u63cf\u8ff0\u4e4b\u95f4\u5efa\u7acb\u6865\u6881\uff0c\u4ece\u800c\u53ef\u4ee5\u770b\u5230\u751f\u7269\u529f\u80fd\u5982\u4f55\u5728\u4e0d\u540c\u5c3a\u5ea6\u4e0a\u5b9e\u73b0 [12,151,153,209]\u3002 <\/span><\/section>\n

<\/section>\n


<\/p>\n

\n
\n
\n

\u53c2\u8003\u6587\u732e<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n
\n
\n
\n
    \n
  1. \n

    Anderson, P.W.: More if different: Broken Symmetry and the nature of hierarchical structure in sci- ence. Science 177, 393\u2013396 (1972)<\/p>\n<\/li>\n

  2. \n

    Laughlin, R.B., Pines, D., Schmalian, J., Stojkovic, B.P., Wolynes, P.: The middle way. Proc. Natl. Acad. Sci. USA 97, 32\u201337 (2000)<\/p>\n<\/li>\n

  3. \n

    Qian, H., Ao, P., Tu, Y.H., Wang, J.: A framework towards understanding mesoscopic phenomena: emesrgent unpredictability, symmetry breaking and dynamics across scales. Chem. Phys. Lett. 665, 153\u2013161 (2016)<\/p>\n<\/li>\n

  4. \n

    Hopfield, J.J.: Physics, computation, and why biology looks so different. J. Theor. Biol. 171, 53\u201360 (1994)<\/p>\n<\/li>\n

  5. \n

    Fang, X., Kruse, K., Lu, T., Wang, J.: Nonequilibrium physics in biology. Rev. Mod. Phys. 91, 045004 (2019)<\/p>\n<\/li>\n

  6. \n

    Wang, J.: Landscape and flux theory of non-equilibrium dynamical systems with application to biol- ogy. Adv. Phys. 64, 1\u2013137 (2015)<\/p>\n<\/li>\n

  7. \n

    Frauenfelder, H., Parak, F., Young, R.D.: Conformational substates in proteins. Annu. Rev. Biophys Biophy. Chem. 17, 451 (1988)<\/p>\n<\/li>\n

  8. \n

    Frauenfelder, H., Sligar, S., Wolynes, P.: The energy landscapes and motions of proteins. Science 254, 1598\u20131603 (1991)<\/p>\n<\/li>\n

  9. \n

    Frauenfelder, H., Wolynes, P.G.: Biomolecules: where the physics of complexity and simplicity meet. Phys. Today. 47, 58\u201364 (1994)<\/p>\n<\/li>\n

  10. \n

    Austin, R.H., Beeson, K.W., Eisenstein, L., Frauenfelder, H., Gunsalus, I.C.: Dynamics of ligand binding to myoglobin. Biochemistry 14, 5355\u20135373 (1975)<\/p>\n<\/li>\n

  11. \n

    Chu, X., Wang, J.: Specificity and affinity quantification of flexible recognition from underlying energy landscape topography. PLOS Comp. Biol. 10, e1003782 (2014)<\/p>\n<\/li>\n

  12. \n

    Chu, X., Wang, J.: Microscopic chromosomal structural and dynamical origin of cell differentiation and reprogramming. Adv. Sci. 7, 2001572 (2020)<\/p>\n<\/li>\n

  13. \n

    Frauenfelder, H., Petsko, G.A., Tsernoglou, D.: Temperature-dependent X-ray diffraction as a probe of protein structural dynamics. Nature 280, 558\u2013563 (1979)<\/p>\n<\/li>\n

  14. \n

    Levinthal, C.: Mossbauer Spectroscopy in Biological Systems: Proceedings of a Meeting Held at Allerton House, Monticello, Illinois. Debrunner P., Tsibris J., Munck E, Proceedings of a meeting held at Allerton House, pp. 22\u201324 (1969)<\/p>\n<\/li>\n

  15. \n

    Wang, J., Verkhivker, G.M.: Energy landscape theory, funnels, specificity, and optimal criterion of biomolecular binding. Phys. Rev. Lett. 90, 188101 (2003)<\/p>\n<\/li>\n

  16. \n

    Bryngelson, J.D., Onuchic, J.N., Socci, N.D., Wolynes, P.G.: Funnels, pathways, and the energy land- scape of protein folding: a synthesis. Proteins Struct. Funct. Bioinform. 21, 167\u2013195 (1995)<\/p>\n<\/li>\n

  17. \n

    Onuchic, J.N., Luthey-Schulten, Z., Wolynes, P.G.: Theory of protein folding: the energy landscape perspective. Annu. Rev. Phys. Chem. 48, 545\u2013600 (1997)<\/p>\n<\/li>\n

  18. \n

    Dill, K.A., Chan, H.S.: From Levinthal to pathways to funnels. Nat. Struct. Biol. 4, 10\u201319 (1997)<\/p>\n<\/li>\n

  19. \n

    Wang, J., Oliveira, R.J., Chu, X.K., Whitford, P.C., Chahine, J., Han, W., Wang, E.K., Onuchic, J.N., Leite, V.B.P.: Topography of funneled landscapes determines the thermodynamics and kinetics of protein folding. Proc. Natl. Acad. Sci. USA 109, 15763\u201315768 (2012)<\/p>\n<\/li>\n

  20. \n

    Chu, X.K., Gan, L.F., Wang, E.K., Wang, J.: Quantifying the topography of the intrinsic energy land- scape of flexible biomolecular recognition. Proc. Natl. Acad. Sci. USA 110, E2342\u2013E2351 (2013)<\/p>\n<\/li>\n

  21. \n

    Wang, J., Zheng, X., Yang, Y., Drueckhammer, D., Wei, Y., Verkhivker, G., Wang, E.: Quantifying intrinsic specificity: a potential complement to affinity in drug screening. Phys. Rev. Lett. 99, 198101 (2007)<\/p>\n<\/li>\n

  22. \n

    Yan, Z., Zheng, X., Wang, E., Wang, J.: Thermodynamic and kinetic specificities of ligand binding. Chem. Sci. 4, 2387\u20132395 (2013)<\/p>\n<\/li>\n

  23. \n

    Zheng, X.L., Liu, Z.J., Li, D., Wang, E.K., Wang, J.: Rational drug design: the search for ras protein hydrolysis intermediate conformation inhibitors with both affinity and specificity. Curr. Pharm. Des. 19, 2246\u20132258 (2013)<\/p>\n<\/li>\n

  24. \n

    Yan, Z.Q., Wang, J.: Quantifying the kinetic residence time as a potential complement to affinity for the aptamer selection. J. Phys. Chem. B 122, 8380\u20138385 (2018)<\/p>\n<\/li>\n

  25. \n

    Yan, Z., Wang, J.: Incorporating specificity into optimization: evaluation of SPA using CSAR 2014 and CASF 2013 benchmarks. J. Comput. Aid. Mol. Des. 30, 219\u2013227 (2016)<\/p>\n<\/li>\n

  26. \n

    Yan, Z., Wang, J.: Specificity quantification of biomolecular recognition and its implication for drug discovery. Sci. Rep. 2, 309 (2012)<\/p>\n<\/li>\n

  27. \n

    Zheng, X.L., Gan, L.F., Wang, E.K., Wang, J.: Pocket-based drug design: exploring pocket space. Aaps J. 15, 228\u2013241 (2013)<\/p>\n<\/li>\n

  28. \n

    Zheng, X.L., Wang, J.: The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition. PLOS Comput. Biol. 11, 24 (2015)<\/p>\n<\/li>\n

  29. \n

    Zheng, X.L., Wang, J.: Universal statistical fluctuations in thermodynamics and kinetics of single molecular recognition. Phys. Chem. Chem. Phys. 18, 8570\u20138578 (2016)<\/p>\n<\/li>\n

  30. \n

    Yan, Z., Guo, L., Hu, L., Wang, J.: Specificity and affinity quantification of protein-protein interac- tions. Bioinformatics 29, 1127\u20131133 (2013)<\/p>\n<\/li>\n

  31. \n

    Yan, Z., Wang, J.: Optimizing scoring function of protein-nucleic acid interactions with both affinity and specificity. PLoS ONE 8, e74443 (2012)<\/p>\n<\/li>\n

  32. \n

    Yan, Z., Wang, J.: Optimizing the affinity and specificity of ligand binding with the inclusion of sol- vation effect. Proteins Struct. Funct. Bioinform. 83, 1632\u20131642 (2015)<\/p>\n<\/li>\n

  33. \n

    Yang, Y.L., Li, G.H., Zhao, D.Y., Yu, H.Y., Zheng, X.L., Peng, X.D., Zhang, X., Fu, T., Hu, X.Q., Niu, M.S., Ji, X.F., Zou, L.B., Wang, J.: Computational discovery and experimental verification of tyrosine kinase inhibitor pazopanib for the reversal of memory and cognitive deficits in rat model neurodegeneration. Chem. Sci. 6, 2812\u20132821 (2015)<\/p>\n<\/li>\n

  34. \n

    Zhao, W.J., Li, D., Liu, Z.J., Zheng, X.L., Wang, J., Wang, E.K.: Spiclomazine induces apoptosis associated with the suppression of cell viability, migration and invasion in pancreatic carcinoma cells. PLoS ONE 8, 10 (2013)<\/p>\n<\/li>\n

  35. \n

    Liu, Z., Li, D., Zhao, W., Zheng, X., Wang, E.: A potent lead induces apoptosis in pancreatic cancer cells. PLoS ONE 7, e37841 (2012)<\/p>\n<\/li>\n

  36. \n

    Liu, Z., Zheng, X., Yang, X., Wang, E., Wang, J.: Affinity and specificity of levamlodipine-human serum albumin interactions: insights into its carrier function. Biophys. J. 96, 3917\u20133925 (2009)<\/p>\n<\/li>\n

  37. \n

    Liu, Z.J., Li, D., Zheng, X.L., Wang, E.K., Wang, J.: Selective induction of apoptosis: promising therapy in pancreatic cancer. Curr. Pharm. Des. 19, 2259\u20132268 (2013)<\/p>\n<\/li>\n

  38. \n

    Liu, Z.J., Zheng, X.L., Wang, J., Wang, E.K.: Molecular analysis of thymopentin binding to HLA-DR molecules. PLoS ONE 2, 8 (2007)<\/p>\n<\/li>\n

  39. \n

    Li, D., Liu, Z.J., Zhao, W.J., Zheng, X.L., Wang, J., Wang, E.K.: A small-molecule induces apoptosis and suppresses metastasis in pancreatic cancer cells. Eur. J. Pharm. Sci. 48, 658\u2013667 (2013)<\/p>\n<\/li>\n

  40. \n

    Liu, F., Chu, X., Lu, H.P., Wang, J.: Molecular mechanism of multispecific recognition of Calmodulin through conformational changes. Proc. Natl. Acad. Sci. USA 114, E3927\u2013E3934 (2017)<\/p>\n<\/li>\n

  41. \n

    Liu, F., Qing, H., Wang, J.: Mechanochemical model of the power stroke of the single-headed motor protein KIF1A. J. Phys. Chem. B 122, 11002\u201311013 (2018)<\/p>\n<\/li>\n

  42. \n

    Wang, Y., Chu, X.K., Longhi, S., Roche, P., Han, W., Wang, E.K., Wang, J.: Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in mea- sles virus nucleoprotein. Proc. Natl. Acad. Sci. USA 110, E3743\u2013E3752 (2013)<\/p>\n<\/li>\n

  43. \n

    Wang, Y., Chu, X.K., Suo, Z.C., Wang, E.K., Wang, J.: Multidomain protein solves the folding prob- lem by multifunnel combined landscape: theoretical investigation of a Y-family DNA polymerase. J. Am. Chem. Soc. 134, 13755\u201313764 (2012)<\/p>\n<\/li>\n

  44. \n

    Chu, X., Liu, F., Maxwell, B.A., Wang, Y., Suo, Z., Wang, H., Han, W., Wang, J.: Dynamic confor- mational change regulates the protein-DNA recognition: an investigation on binding of a Y-family polymerase to its target DNA. PLoS Comput. Biol. 10, e1003804 (2014)<\/p>\n<\/li>\n

  45. \n

    Yan, Z., Wang, J.: Funneled energy landscape unifies principles of protein binding and evolution. Proc. Natl. Acad. Sci. USA 117, 27218\u201327223 (2020)<\/p>\n<\/li>\n

  46. \n

    Yan, Z., Wang, J.: Superfunneled energy landscape of protein evolution unifies the principles of pro- tein evolution, folding, and design. Phys. Rev. Lett. 122, 018103 (2019)<\/p>\n<\/li>\n

  47. \n

    Yan, Z., Wang, J.: SPA-LN: a scoring function of ligand\u2013nucleic acid interactions via optimizing both specificity and affinity. Nucleic Acids Res. 45, e110 (2017)<\/p>\n<\/li>\n

  48. \n

    Kar, G., Keskin, O., Gursoy, A., Nussinov, R.: Allostery and population shift in drug discovery. Curr. Opin. Pharmacol. 10, 715\u2013722 (2010)<\/p>\n<\/li>\n

  49. \n

    Dunker, A.K., Lawson, J.D., Brown, C.J., Williams, R.M., Romero, P., Oh, J.S., Oldfield, C.J., Campen, A.M., Ratliff, C.M., Hipps, K.W.: Intrinsically disordered protein. J. Mol. Graph. Model. 19, 26\u201359 (2001)<\/p>\n<\/li>\n

  50. \n

    Onuchic, J.N., Levy, Y., Wolynes, P.G.: Fly-casting in protein? DNA binding:? Frustration between protein folding and electrostatics facilitates target recognition. J. Am. Chem. Soc. 129, 738\u2013739 (2007)<\/p>\n<\/li>\n

  51. \n

    Levy, Y., Wolynes, P.G., Onuchic, J.N.: Protein topology determines binding mechanism. Proc. Natl. Acad. Sci. USA 101, 511\u2013516 (2004)<\/p>\n<\/li>\n

  52. \n

    Wang, J., Xu, L., Wang, E.: Optimal specificity and function for flexible biomolecular recognition. Biophys. J. 92, L109\u2013L111 (2007)<\/p>\n<\/li>\n

  53. \n

    Zhao, L.C., Lu, H.P., Wang, J.: Exploration of multistate conformational dynamics upon ligand bind- ing of a monomeric enzyme involved in pyrophosphoryl transfer. J. Phys. Chem. B 122, 1885\u20131897 (2018)<\/p>\n<\/li>\n

  54. \n

    Zhao, L.C., Suarez, I.P., Gauto, D.F., Rasia, R.M., Wang, J.: The key role of electrostatic interactions in the induced folding in RNA recognition by DCL1-A. Phys. Chem. Chem. Phys. 20, 9376\u20139388 (2018)<\/p>\n<\/li>\n

  55. \n

    Chu, X.K., Suo, Z.C., Wang, J.: Investigating the trade-off between folding and function in a multid- omain Y-family DNA polymerase. Elife 9, 40 (2020)<\/p>\n<\/li>\n

  56. \n

    Chu, X.K., Suo, Z.C., Wang, J.: Confinement and crowding effects on folding of a multidomain Y-family DNA polymerase. J. Chem. Theory. Comput. 16, 1319\u20131332 (2020)<\/p>\n<\/li>\n

  57. \n

    Chu, X.K., Wang, J.: Position-, disorder-, and salt-dependent diffusion in binding-coupled-folding of intrinsically disordered proteins. Phys. Chem. Chem. Phys. 21, 5634\u20135645 (2019)<\/p>\n<\/li>\n

  58. \n

    Chu, X.K., Wang, Y., Gan, L.F., Bai, Y.W., Han, W., Wang, E.K., Wang, J.: Importance of electro- static interactions in the association of intrinsically disordered histone chaperone Chz1 and histone H2A.Z-H2B. PLOS Comput. Biol. 8, 11 (2012)<\/p>\n<\/li>\n

  59. \n

    Chu, W.T., Chu, X., Wang, J.: Investigations of the underlying mechanisms of HIF-1\u03b1 and CITED2 binding to TAZ1. Proc. Natl. Acad. Sci. USA 117, 201915333 (2020)<\/p>\n<\/li>\n

  60. \n

    Chu, W.T., Chu, X.K., Wang, J.: Binding mechanism and dynamic conformational change of C subu- nit of PKA with different pathways. Proc. Natl. Acad. Sci. USA 114, E7959\u2013E7968 (2017)<\/p>\n<\/li>\n

  61. \n

    Chu, W.T., Clarke, J., Shammas, S.L., Wang, J.: Role of non-native electrostatic interactions in the coupled folding and binding of PUMA with Mcl-1. PLOS Comput. Biol. 13, 20 (2017)<\/p>\n<\/li>\n

  62. \n

    Chu, W.T., Nesbitt, N.M., Gnatenko, D.V., Li, Z., Zhang, B., Seeliger, M.A., Browne, S., Mantle, T.J., Bahou, W.F., Wang, J.: Enzymatic activity and thermodynamic stability of biliverdin IX\u03b2 reductase are maintained by an active site serine. Chem. Eur. J. 23, 1891\u20131900 (2017)<\/p>\n<\/li>\n

  63. \n

    Chu, W.T., Shammas, S.L., Wang, J.: Charge interactions modulate the encounter complex ensemble of two differently charged disordered protein partners of KIX. J. Chem. Theory. Comput. 16, 3856\u2013 3868 (2020)<\/p>\n<\/li>\n

  64. \n

    Chu, W.T., Suo, Z.C., Wang, J.: Binding-induced conformational changes involved in sliding clamp PCNA and DNA polymerase DPO4. Iscience 23, 24 (2020)<\/p>\n<\/li>\n

  65. \n

    Chu, W.T., Wang, J.: Energy landscape topography reveals the underlying link between binding speci- ficity and activity of enzymes. Sci. Rep. 6, 9 (2016)<\/p>\n<\/li>\n

  66. \n

    Chu, W.T., Wang, J.: Quantifying the intrinsic conformation energy landscape topography of proteins with large-scale open-closed transition. ACS Cent. Sci. 4, 1015\u20131022 (2018)<\/p>\n<\/li>\n

  67. \n

    Chu, W.T., Wang, J.: Thermodynamic and sequential characteristics of phase separation and droplet formation for an intrinsically disordered region\/protein ensemble. PLOS Comput. Biol. 17, 20 (2021)<\/p>\n<\/li>\n

  68. \n

    Chu, W.T., Wang, J.: Influence of sequence length and charged residues on Swc5 binding with histone H2A\u2013H2B. Proteins Struct. Funct. Bioinform. 89, 512\u2013520 (2021)<\/p>\n<\/li>\n

  69. \n

    Van Kampen, N.G.: Stochastic Processes in Physics and Chemistry, 3rd edn. Elsevier, Amsterdam (2007)<\/p>\n<\/li>\n

  70. \n

    Reichl, L.E.: A Modern Course in Statistical Physics, 3rd Revised and Updated Edition. University of Texas Press, Texas (1984)<\/p>\n<\/li>\n

  71. \n

    Swain, P.S., Elowitz, M.B., Siggia, E.D.: Intrinsic and extrinsic contributions to stochasticity in gene expression. Proc. Natl. Acad. Sci. USA 99, 12795\u201312795 (2002)<\/p>\n<\/li>\n

  72. \n

    Hu, G.: Stochastic Force and Nonlinear Systems. Shanghai Science Education, Shanghai (1995)<\/p>\n<\/li>\n

  73. \n

    Gillespie, D.T.: A general method for numerically simulating the stochastic time evolution of coupled chemical reactions. J. Computat. Phys. 22, 403\u2013434 (1976)<\/p>\n<\/li>\n

  74. \n

    Haken, H.: Advanced Synergetics: Instability Hierarchies of Self-Organizing Systems and Devices. Springer, Berlin (1983)<\/p>\n<\/li>\n

  75. \n

    Wang, J., Xu, L., Wang, E.K.: Potential landscape and flux framework of nonequilibrium networks: Robustness, dissipation, and coherence of biochemical oscillations. Proc. Natl. Acad. Sci. USA 105, 12271\u201312276 (2008)<\/p>\n<\/li>\n

  76. \n

    Xu, L., Wang, J.: Quantifying the potential and flux landscapes of multi-locus evolution. J. Theor. Biol. 422, 31\u201349 (2017)<\/p>\n<\/li>\n

  77. \n

    Xu, L., Wang, J.: Landscape and flux for quantifying global stability and dynamics of game theory. PLoS ONE 13, e0201130 (2018)<\/p>\n<\/li>\n

  78. \n

    Xu, L., Wang, J.: Curl flux as a dynamical origin of the bifurcations\/phase transitions of nonequilib- rium systems: cell fate decision making. J. Phys. Chem. B 124, 2549\u20132559 (2020)<\/p>\n<\/li>\n

  79. \n

    Xu, L., Zhang, F., Wang, E.K., Wang, J.: The potential and flux landscape, Lyapunov function and non-equilibrium thermodynamics for dynamic systems and networks with an application to signal- induced Ca2+ oscillation. Nonlinearity 26, R69\u2013R84 (2013)<\/p>\n<\/li>\n

  80. \n

    Xu, L., Zhang, F., Zhang, K., Wang, E.K., Wang, J.: The potential and flux landscape theory of ecol- ogy. PLoS ONE 9, e86746 (2014)<\/p>\n<\/li>\n

  81. \n

    Xu, L., Zhang, K., Wang, J.: Exploring the mechanisms of differentiation, dedifferentiation, repro- gramming and transdifferentiation. PLoS ONE 9, e105216 (2014)<\/p>\n<\/li>\n

  82. \n

    Zhang, F., Xu, L., Zhang, K., Wang, E.K., Wang, J.: The potential and flux landscape theory of evolu- tion. J. Chem. Phys. 137, 065102 (2012)<\/p>\n<\/li>\n

  83. \n

    Gardiner, C.W.: Handbook of Stochastic Methods, Stochastic Processes in Physics & Chemistry. Elsevier, New York (1985)<\/p>\n<\/li>\n

  84. \n

    Haken, H.: Advanced Synergetics: Instability Hierarchies of Self-Organizing Systems and Devices. Springer, Berlin (1987)<\/p>\n<\/li>\n

  85. \n

    Wang, J., Zhang, K., Lu, H.Y., Wang, E.K.: Dominant Kinetic Paths on Biomolecular Binding- Folding Energy Landscape. Phys. Rev. Lett. 96, 168101 (2006)<\/p>\n<\/li>\n

  86. \n

    Wang, J., Zhang, K., Wang, E.: Kinetic paths, time scale, and underlying landscapes: a path inte- gral framework to study global natures of nonequilibrium systems and networks. J. Chem. Phys. 133, 125103 (2010)<\/p>\n<\/li>\n

  87. \n

    Feng, H.D., Han, B., Wang, J.: Dominant kinetic paths of complex systems: gene networks. J Phys. Chem. Lett. 1, 1836\u20131840 (2010)<\/p>\n<\/li>\n

  88. \n

    Feng, H.D., Zhang, K., Wang, J.: Non-equilibrium transition state rate theory. Chem. Sci. 5, 3761\u2013 3769 (2014)<\/p>\n<\/li>\n

  89. \n

    Wang, J., Xu, L., Wang, E.K., Huang, S.: The potential landscape of genetic circuits imposes the arrow of time in stem cell differentiation. Biophys. J. 99, 29\u201339 (2010)<\/p>\n<\/li>\n

  90. \n

    Wang, J., Zhang, K., Lu, H.Y., Wang, E.K.: Quantifying kinetic paths of protein folding. Biophys. J. 89, 1612\u20131620 (2005)<\/p>\n<\/li>\n

  91. \n

    Yan, H., Wang, J.: Quantification of motor network dynamics in Parkinson\u2019s disease by means of landscape and flux theory. PLoS ONE 12, e0174364 (2017)<\/p>\n<\/li>\n

  92. \n

    Yan, H., Zhang, K., Wang, J.: Physical mechanism of mind changes and tradeoffs among speed, accuracy, and energy cost in brain decision making: landscape, flux, and path perspectives. Chi- nese Phys B. 25, 078702 (2016)<\/p>\n<\/li>\n

  93. \n

    Yan, H., Zhao, L., Hu, L., Wang, X., Wang, E., Wang, J.: Nonequilibrium landscape theory of neu- ral networks. Proc. Natl. Acad. Sci. USA 110, E4185\u2013E4194 (2013)<\/p>\n<\/li>\n

  94. \n

    Wang, J., Huang, B., Xia, X., Sun, Z.: Funneled landscape leads to robustness of cell networks: yeast cell cycle. PLOS Comput. Biol. 2, e147 (2006)<\/p>\n<\/li>\n

  95. \n

    Xu, L.F., Shi, H.L., Feng, H.D., Wang, J.: The energy pump and the origin of the non-equilibrium flux of the dynamical systems and the networks. J. Chem. Phys. 136, 165102 (2012)<\/p>\n<\/li>\n

  96. \n

    G\u00e9rard, C., Goldbeter, A.: Temporal self-organization of the cyclin\/Cdk network driving the mam- malian cell cycle. Proc. Natl. Acad. Sci. USA 106, 21643\u201321648 (2009)<\/p>\n<\/li>\n

  97. \n

    Lv, C., Li, X., Li, F., Li, T.: Energy landscape reveals that the budding yeast cell cycle is a robust and adaptive multi-stage process. PLoS Comput. Biol. 11, e1004156 (2015)<\/p>\n<\/li>\n

  98. \n

    Ferrell, J., Tsai, T.C., Yang, Q.: Modeling the cell cycle: why do certain circuits oscillate? Cell<\/p>\n<\/li>\n

  99. \n

    144, 874\u2013885 (2011)<\/p>\n<\/li>\n

  100. \n

    Bo, H., Jin, W.: Quantifying robustness and dissipation cost of yeast cell cycle network: the fun- neled energy landscape perspectives. Biophys. J. 92, 3755\u20133763 (2007)<\/p>\n<\/li>\n

  101. \n

    Yang, Q., Ferrell, J.E., Jr.: The Cdkl-APC\/C cell cycle oscillator circuit functions as a time delayed, ultra sensitive switch. Nat. Cell Biol. 15, 519 (2013)<\/p>\n<\/li>\n

  102. \n

    Tsai, Y.C., Theriot, J.A., Ferrell, J.E.: Changes in oscillatory dynamics in the cell cycle of early<\/p>\n<\/li>\n

  103. \n

    Xenopus laevis embryos. PLoS Biol. 12, e1001788 (2014)<\/p>\n<\/li>\n

  104. \n

    Li, F., Long, T., Lu, Y., Ouyang, Q., Tang, C.: The yeast cell-cycle is robustly designed. Proc. Natl. Acad. Sci. USA 101, 4781\u20134786 (2004)<\/p>\n<\/li>\n

  105. \n

    Li, C.H., Wang, J.: Landscape and flux reveal a new global view and physical quantification of mammalian cell cycle. Proc. Natl. Acad. Sci. USA 111, 14130\u201314135 (2014)<\/p>\n<\/li>\n

  106. \n

    Han, B., Wang, J.: Quantifying robustness and dissipation cost of yeast cell cycle network: The funneled energy landscape perspectives. Biophys. J. 92, 3755\u20133763 (2007)<\/p>\n<\/li>\n

  107. \n

    Wang, J., Li, C.H., Wang, E.K.: Potential and flux landscapes quantify the stability and robustness of budding yeast cell cycle network. Proc. Natl. Acad. Sci. USA 107, 8195\u20138200 (2010)<\/p>\n<\/li>\n

  108. \n

    Zhang, K., Wang, J.: Exploring the underlying mechanisms of the Xenopus laevis embryonic cell cycle. J. Phys. Chem. B 122, 5487\u20135499 (2018)<\/p>\n<\/li>\n

  109. \n

    Kauffman, S.: Homeostasis and differentiation in random genetic control networks. Nature 224, 177\u2013178 (1969)<\/p>\n<\/li>\n

  110. \n

    Kauffman, S.: Differentiation of malignant to benign cells. J. Theor. Biol. 31, 429\u2013451 (1971)<\/p>\n<\/li>\n

  111. \n


    <\/p>\n<\/li>\n

  112. \n

    Zhang, B., Wolynes, P.G.: Stem cell differentiation as a many-body problem. Proc. Natl. Acad. Sci. USA 111, 10185\u201310190 (2014)<\/p>\n<\/li>\n

  113. \n

    Waddington, C.H.: The strategy of the genes. A discussion of some aspects of theoretical biology. With an appendix by H. Kacser (1957)<\/p>\n<\/li>\n

  114. \n

    Chickarmane, V., Peterson, C.: A computational model for understanding stem cell, trophectoderm and endoderm lineage determination. PLoS ONE 3, e3478 (2008)<\/p>\n<\/li>\n

  115. \n

    Jiang, J.M., Chan, Y.S., Loh, Y.H., Cai, J., Tong, G.Q., Lim, C.A., Robson, P., Zhong, S., Ng, H.H.: A core Klf circuitry regulates self-renewal of embryonic stem cells. Nat. Cell Biol. 10, 353\u2013360 (2008)<\/p>\n<\/li>\n

  116. \n

    Sui, H., Ernberg, I., Kauffman, S.: Cancer attractors: a systems view of tumors from a gene network dynamics and developmental perspective. Semin. Cell Dev. Biol. 20, 869\u2013876 (2009)<\/p>\n<\/li>\n

  117. \n

    Li, C.H., Wang, J.: Quantifying cell fate decisions for differentiation and reprogramming of a human stem cell network: landscape and biological paths. PLOS Comput. Biol. 9, e1003165 (2013)<\/p>\n<\/li>\n

  118. \n

    Wang, J., Zhang, K., Xu, L., Wang, E.: Quantifying the Waddington landscape and biological paths for development and differentiation. Proc. Natl. Acad. Sci. USA 108, 8257\u20138262 (2011)<\/p>\n<\/li>\n

  119. \n

    Zhang, K., Wang, J.: Exploring the underlying mechanisms of the coupling between cell differentia- tion and cell cycle. J. Phys. Chem. B 123, 3490\u20133498 (2019)<\/p>\n<\/li>\n

  120. \n

    Li, C.H., Wang, J.: Quantifying Waddington landscapes and paths of non-adiabatic cell fate decisions for differentiation, reprogramming and transdifferentiation. J. R. Soc. Interface 10, 20130787 (2013)<\/p>\n<\/li>\n

  121. \n

    Feng, H.D., Wang, J.: A new mechanism of stem cell differentiation through slow binding\/unbinding of regulators to genes. Sci. Rep. 2, 550 (2012)<\/p>\n<\/li>\n

  122. \n

    Weinberg, H.: Hallmarks of cancer: the next generation. Cell 144, 646\u2013674 (2011)<\/p>\n<\/li>\n

  123. \n

    Hanahan, D., Weinberg, R.A.: The hallmarks of cancer. Cell 100, 57\u201370 (2000)<\/p>\n<\/li>\n

  124. \n

    Gatenby, R.A., Vincent, T.L.: An evolutionary model of carcinogenesis. Cancer Res. 63, 6212\u20136220 (2003)<\/p>\n<\/li>\n

  125. \n

    Wang, E., Lenferink, A., Connor-McCourt, M.O.: Cancer systems biology: exploring cancer-associated genes on cellular networks. Cell Mol. Life Sci. 64, 1752\u20131762 (2007)<\/p>\n<\/li>\n

  126. \n

    Ao, P., Galas, D., Hood, L., Zhu, X.M.: Cancer as robust intrinsic state of endogenous molecular- cellular network shaped by evolution. Med Hypotheses. 70, 678\u2013684 (2008)<\/p>\n<\/li>\n

  127. \n

    Bar-Yam, Y., Harmon, D., Bivort, B.D.: Systems biology. Attractors and democratic dynamics. Sci- ence 323, 1016 (2009)<\/p>\n<\/li>\n

  128. \n

    Basan, M., Risler, T., Joanny, J., Sastre Garau, X., Prost, J.: Homeostatic competition drives tumor growth and metastasis nucleation. Hfsp J. 3, 265\u2013272 (2009)<\/p>\n<\/li>\n

  129. \n

    Creixell, P., Schoof, E.M., Erler, J.T., Linding, R.: Navigating cancer network attractors for tumor- specific therapy. Nat. Biotechnol. 30, 842\u2013848 (2012)<\/p>\n<\/li>\n

  130. \n

    Lu, M., Jolly, M.K., Levine, H., Onuchic, J.N., Ben-Jacob, E.: MicroRNA-based regulation of epithe- lial-hybrid-mesenchymal fate determination. Proc. Natl. Acad. Sci. USA 110, 18144\u201318149 (2013)<\/p>\n<\/li>\n

  131. \n

    Yu, C., Liu, Q., Chen, C., Yu, J., Wang, J.: Landscape perspectives of tumor, EMT, and development. Phys. Biol. 16, 051003 (2019)<\/p>\n<\/li>\n

  132. \n

    Yu, C., Wang, J.: A physical mechanism and global quantification of breast cancer. PLoS ONE 11, e0157422 (2016)<\/p>\n<\/li>\n

  133. \n

    Yu, C., Xu, H., Wang, J.: A global and physical mechanism of gastric cancer formation and progres- sion. J. Theor. Biol 520, 110643 (2021)<\/p>\n<\/li>\n

  134. \n

    Li, C.H., Wang, J.: Quantifying the landscape for development and cancer from a core cancer stem cell circuit. Cancer Res. 75, 2607\u20132618 (2015)<\/p>\n<\/li>\n

  135. \n

    Li, W.B., Wang, J.: Uncovering the underlying mechanism of cancer tumorigenesis and development under an immune microenvironment from global quantification of the landscape. J. R. Soc. Interface. 14, 20170105 (2017)<\/p>\n<\/li>\n

  136. \n

    Chen, C., Wang, J.: A physical mechanism of cancer heterogeneity. Sci. Rep. 6, 20679 (2015)<\/p>\n<\/li>\n

  137. \n

    Li, C., Wang, J.: Quantifying the underlying landscape and paths of cancer. J. R. Soc. Interface. 11, 20140774 (2014)<\/p>\n<\/li>\n

  138. \n

    Kang, X., Li, C.: A dimension reduction approach for energy landscape: identifying intermediate states in metabolism-MT network. Adv. Sci. 8, 2003133 (2021)<\/p>\n<\/li>\n

  139. \n

    Hopfield, J.J.: Neural networks and physical systems with emergent collective computational abilities. Proc. Natl. Acad. Sci. USA 79, 2554\u20132558 (1982)<\/p>\n<\/li>\n

  140. \n

    Shadlen, M.N., Newsome, W.T.: Neural basis of a perceptual decision in the parietal cortex (area LIP) of the rhesus monkey. J. Neurophysiol. 86, 1916 (2001)<\/p>\n<\/li>\n

  141. \n

    Roitman, J.D., Shadlen, M.N.: Response of neurons in the lateral intraparietal area during a combined visual discrimination reaction time task. J. Neurosci. 22, 9475\u20139489 (2002)<\/p>\n<\/li>\n

  142. \n

    Abbott, L.F.: Theoretical neuroscience rising. Neuron 60, 489\u2013495 (2008)<\/p>\n<\/li>\n

  143. \n


    <\/p>\n<\/li>\n

  144. \n

    Yan, H., Wang, J.: Non-equilibrium landscape and flux reveal the stability-flexibility-energy tradeoff in working memory. PLOS Comp. Biol. 16, e1008209 (2020)<\/p>\n<\/li>\n

  145. \n

    Han, Y., Wang, J.: Non-equilibrium landscape and flux reveal how the central amygdala circuit gates passive and active defensive responses. J. R. Soc. Interface. 16, 20180756 (2019)<\/p>\n<\/li>\n

  146. \n

    Fisher, R.A.: The Genetical Theory of Natural Selection. Oxford University Press, Oxford (1930)<\/p>\n<\/li>\n

  147. \n

    Rice, S.H.: Evolutionary Theory: Mathematical and Conceptual Foundations. Sinauer Associates, Massachusetts (2004)<\/p>\n<\/li>\n

  148. \n

    Wright, S.: Statistical genetics and evolution. B. Am. Math. Soc. 48, 223\u2013246 (1941)<\/p>\n<\/li>\n

  149. \n

    Shraiman, R.A.N., Boris, I.: Statistical genetics and evolution of quantitative traits. Rev. Mod. Phys.<\/p>\n<\/li>\n

  150. \n

    83, 1283\u20131300 (2011)<\/p>\n<\/li>\n

  151. \n

    Valen, L.V.: A new evolutionary law. Evolut. Theory 1, 1\u201330 (1973)<\/p>\n<\/li>\n

  152. \n

    Tokuda, N., Terada, T.P., Sasai, M.: Dynamical modeling of three-dimensional genome organization in interphase budding yeast. Biophys. J. 102, 296\u2013304 (2012)<\/p>\n<\/li>\n

  153. \n

    others, E. P. C. a.: An integrated encyclopedia of DNA elements in the human genome OPEN. Nature<\/p>\n<\/li>\n

  154. \n

    489, 57\u201374 (2012)<\/p>\n<\/li>\n

  155. \n

    Pruitt, K.D., Tatusova, T., Maglott, D.R.: NCBI Reference Sequences (RefSeq): a curated non-redundant sequence database of genomes, transcripts and proteins. Nucleic Acids Res. 33, D501\u2013D504 (2005)<\/p>\n<\/li>\n

  156. \n

    Lieberman-Aiden, E., Berkum, N.V., Williams, L., Imakaev, M., Ragoczy, T., Telling, A., Amit, I., Lajoie, B.R., Sabo, P.J., Dorschner, M.O.: Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289 (2009)<\/p>\n<\/li>\n

  157. \n

    Pierro, M., Cheng, R.R., Aiden, E.L., Wolynes, P.G., Onuchic, J.N.: De novo prediction of human chromosome structures: epigenetic marking patterns encode genome architecture. Proc. Natl. Acad. Sci. USA 114, 201714980 (2017)<\/p>\n<\/li>\n

  158. \n

    Yang, H., Luan, Y., Liu, T., Lee, H.J., Yue, F.: A map of cis-regulatory elements and 3D genome structures in zebrafish. Nature 588, 337\u2013343 (2020)<\/p>\n<\/li>\n

  159. \n

    Chu, X., Wang, J.: Conformational state switching and pathways of chromosome dynamics in cell cycle. Appl. Phys. Rev. 7, 031403 (2020)<\/p>\n<\/li>\n

  160. \n

    Chu, X., Wang, J.: Insights into the molecular mechanisms of cell fate decision making processes from chromosome structural dynamics. bioRxiv, 2021.05.09.443292 (2021)<\/p>\n<\/li>\n

  161. \n

    Chu, X., Wang, J.: Deciphering the molecular mechanism of the cancer formation by chromosome structural dynamics. bioRxiv, 2021.02.15.431330 (2021)<\/p>\n<\/li>\n

  162. \n

    Nicolis, G., Prigogine, I.: Self-Organization in Nonequilibrium Systems. Wiley, New York (1977)<\/p>\n<\/li>\n

  163. \n

    Fang, X., Liu, Q., Christopher, B., Zach, H., Han, W., Jin, W., Jie, X.: Cell fate potentials and switch- ing kinetics uncovered in a classic bistable genetic switch. Nat. Commun. 9, 2787 (2018)<\/p>\n<\/li>\n

  164. \n

    Jiang, Z., Tian, L., Fang, X., Zhang, K., Liu, Q., Dong, Q., Wang, E., Wang, J.: The emergence of the two cell fates and their associated switching for a negative auto-regulating gene. BMC Biol. 17, 49 (2019)<\/p>\n<\/li>\n

  165. \n

    Ptashne, M.: A Genetic Switch: Phage Lambda Revisited. Cold Spring Harbor Laboratory Press, Cold Spring Harbor (2004)<\/p>\n<\/li>\n

  166. \n

    Liu, Q., Wang, J.: Quantifying the flux as the driving force for nonequilibrium dynamics and ther- modynamics in non-Michaelis\u2013Menten enzyme kinetics. Proc. Natl. Acad. Sci. USA 117, 923\u2013930 (2019)<\/p>\n<\/li>\n

  167. \n

    Nussinov, R., Wolynes, P.G.: A second molecular biology revolution? The energy landscapes of bio- molecular function. Phys. Chem. Chem. Phys. 16, 6321\u20136322 (2014)<\/p>\n<\/li>\n

  168. \n

    Lapidus, S., Han, B., Wang, J.: Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction. Proc. Natl. Acad. Sci. USA 105, 6039\u20136044 (2008)<\/p>\n<\/li>\n

  169. \n

    Wang, J., Zhang, K., Wang, E.: Robustness and dissipation of mitogen-activated protein kinases sig- nal transduction network: Underlying funneled landscape against stochastic fluctuations. J. Chem. Phys. 129, 10B602-109 (2008)<\/p>\n<\/li>\n

  170. \n

    Li, W., Wang, J.: Uncovering the underlying mechanisms of cancer metabolism through the land- scapes and probability flux quantifications. iScience 23, 101 (2020)<\/p>\n<\/li>\n

  171. \n

    Luo, X., Xu, L., Han, B., Wang, J., Morozov, A.V.: Funneled potential and flux landscapes dictate the stabilities of both the states and the flow: Fission yeast cell cycle. PLOS Comput. Biol. 13, e1005710 (2017)<\/p>\n<\/li>\n

  172. \n

    Li, W., Wang, J.: Uncovering the underlying physical mechanism for cancer-immunity of MHC class I diversity. Biochem. Biophys. Res. Commun. 504, 532\u2013537 (2018)<\/p>\n<\/li>\n

  173. \n

    Zhao, L., Wang, J.: Uncovering the mechanisms of Caenorhabditis elegans ageing from global quanti- fication of the underlying landscape. J. R. Soc. Interface. 13, 20160421 (2016)<\/p>\n<\/li>\n

  174. \n

    Li, W., Zhao, L., Wang, J.: Searching for the mechanisms of mammalian cellular aging through underlying gene regulatory networks. Front. Genet. 11, 593 (2020)<\/p>\n<\/li>\n

  175. \n

    Li, C., Wang, E., Wang, J., Sui, H.: Potential landscape and probabilistic flux of a predator prey net- work. PLoS ONE 6, e17888 (2011)<\/p>\n<\/li>\n

  176. \n

    Xu, L., Patterson, D., Staver, A.C., Levine, S.A., Wang, J.: Unifying deterministic and stochastic ecological dynamics via a landscape-flux approach. Proc. Natl. Acad. Sci. USA 118, e2103779118 (2021)<\/p>\n<\/li>\n

  177. \n

    Zhang, K., Wang, J.: Landscape and flux theory of non-equilibrium open economy. Physica A 482, 189\u2013208 (2017)<\/p>\n<\/li>\n

  178. \n

    Zhang, K., Liu, J., Wang, E.K., Wang, J.: Quantifying risks with exact analytical solutions of deriva- tive pricing distribution. Physica A 471, 757\u2013766 (2017)<\/p>\n<\/li>\n

  179. \n

    Zhang, F., Xu, L., Wang, J.: The dynamic and thermodynamic origin of dissipative chaos: chemical Lorenz system. Phys. Chem. Chem. Phys. 22, 27896\u201327902 (2020)<\/p>\n<\/li>\n

  180. \n

    Li, C., Wang, E., Wang, J.: Potential flux landscapes determine the global stability of a Lorenz chaotic attractor under intrinsic fluctuations. J. Chem. Phys. 136, 6681\u20137127 (2012)<\/p>\n<\/li>\n

  181. \n

    Wu, W., Wang, J.: Nonequilibrium thermodynamics of turbulence and stochastic fluid systems. New J. Phys. 22, 113017 (2020)<\/p>\n<\/li>\n

  182. \n

    Wu, W., Zhang, F., Wang, J.: Potential landscape and flux field theory for turbulence and nonequilib- rium fluid systems. Ann Phys-New York. 389, 63\u2013101 (2018)<\/p>\n<\/li>\n

  183. \n

    Zhang, Z., Wang, J.: Curl flux, coherence, and population landscape of molecular systems: Nonequi- librium quantum steady state, energy (charge) transport, and thermodynamics. J. Chem. Phys. 140, 245101 (2014)<\/p>\n<\/li>\n

  184. \n

    Zhang, Z., Wang, J.: Origin of long-lived coherence and excitation dynamics in pigment-protein com- plexes. Sci. Rep. 6, 37629 (2015)<\/p>\n<\/li>\n

  185. \n

    Zhang, Z., Wang, J.: Vibrational and coherence dynamics of molecules. Phys. Chem. Chem. Phys. 17, 23754\u201323760 (2015)<\/p>\n<\/li>\n

  186. \n

    Zhang, Z., Wang, J.: Shape, orientation and magnitude of the curl quantum flux, the coherence and the statistical correlations in energy transport at nonequilibrium steady state. New J. Phys. 17, 093021 (2015)<\/p>\n<\/li>\n

  187. \n

    Zhang, Z., Wang, J.: The assistance of molecular vibrations on coherent energy transfer in photosyn- thesis from the view of quantum heat engine. J. Phys. Chem. B 119, 4662\u20134667 (2015)<\/p>\n<\/li>\n

  188. \n

    Zhang, Z., Wang, J.: Landscape, kinetics, paths and statistics of curl flux, coherence, entanglement and energy transfer in non-equilibrium quantum systems. New J. Phys. 17, 043053 (2015)<\/p>\n<\/li>\n

  189. \n

    Wang, Z.H., Wu, W., Cui, G., Wang, J.: Coherence enhanced quantum metrology in a nonequilibrium optical molecule. New J. Phys. 20, 033034 (2018)<\/p>\n<\/li>\n

  190. \n

    Wang, X., Zhang, Z., Wang, J.: Excitation energy transfer under strong laser drive. Phys. Rev. A. 103, 013516 (2021)<\/p>\n<\/li>\n

  191. \n

    Zhang, K., Wu, W., Wang, J.: The influence of equilibrium and nonequilibrium environments on the macroscopic realism through Leggett-Garg inequality. Phys. Rev. A. 101, 052334 (2020)<\/p>\n<\/li>\n

  192. \n

    Zhang, K., Wang, J.: Entanglement versus Bell nonlocality of quantum nonequilibrium steady states. Quantum Inf. Process. 20, 1\u201332 (2021)<\/p>\n<\/li>\n

  193. \n

    Wang, Z.H., Wu, W., Wang, J.: Steady-state entanglement and coherence of two coupled qubits in equilibrium and nonequilibrium environments. Phys. Rev. A. 99, 042320 (2019)<\/p>\n<\/li>\n

  194. \n

    Li, R., Wang, J.: Thermodynamics and kinetics of Hawking-Page phase transition. Phys. Rev. D. 102, 024085 (2020)<\/p>\n<\/li>\n

  195. \n

    Li, R., Wang, J.: Hawking radiation and P v criticality of charged dynamical (Vaidya) black hole in anti-de Sitter space. Phys. Lett. B. 813, 136035 (2021)<\/p>\n<\/li>\n

  196. \n

    Li, R., Wang, J., Wang, Y. Q., Zhang, H.: Nonequilibrium dynamical transition process between excited states of holographic superconductors. J. High Energ. Phys. 59 (2020)<\/p>\n<\/li>\n

  197. \n

    Li, R., Zhang, K., Wang, J.: Thermal dynamic phase transition of Reissner-Nordstr\u00f6m Anti-de Sitter Black Holes on free energy landscape. J High Energ Phys. 90 (2020)<\/p>\n<\/li>\n

  198. \n

    Wang, H., Wang, J.: The Nonequilibrium Back Reaction of Hawking Radiation to a Schwarzschild Black Hole. Adv. High Energy Phys. 9102461 (2020)<\/p>\n<\/li>\n

  199. \n

    Wang, H., Li, X., Wang, J.: Quantifying the potential and flux landscapes for nonequilibrium multi- verse, a new scenario for time arrow. J. High Energ. Phys. 2021, 105 (2021)<\/p>\n<\/li>\n

  200. \n

    Whitehead, A.N.: Process and Reality. Cambridge University Press, Cambridge (1929)<\/p>\n<\/li>\n

  201. \n

    Kaipayil, J.: Relationalism: A Theory of Being. JIP Publications, Bangalore (2009)<\/p>\n<\/li>\n

  202. \n

    Pamanabhan, T.: Gravitation, Foundations and Frontiers. Cambridge University Press, Cambridge (2012)<\/p>\n<\/li>\n

  203. \n

    Jacobson, T.: Thermodynamics of spacetime: the Einstein equation of state. Phys. Rev. Lett. 75, 1260\u20131263 (1995)<\/p>\n<\/li>\n

  204. \n

    Verlinde, E.: On the origin of gravity and the laws of Newton. J. High Energ. Phys. 2011, 029 (2011)<\/p>\n<\/li>\n

  205. \n

    Zeng, Q., Wang, J.: Information landscape and flux, mutual information rate decomposition and con- nections to entropy production. Entropy-Switz 19, 678 (2017)<\/p>\n<\/li>\n

  206. \n

    Zeng, Q., Wang, J.: Non-Markovian nonequilibrium information dynamics. Phys. Rev. E 98, 032123 (2018)<\/p>\n<\/li>\n

  207. \n

    Zeng, Q., Wang, J. : New fluctuation theorems on Maxwell\u2019s demon. Sci. Adv. eabf1807 (2021)<\/p>\n<\/li>\n

  208. \n

    Maldacena, J., Susskind, L.: Cool horizons for entangled black holes. Fortschr. Phys. 61, 781\u2013811 (2013)<\/p>\n<\/li>\n

  209. \n

    Feng, H., Wang, J.: Potential and flux decomposition for dynamical systems and nonequilibrium ther- modynamics: Curvature, gauge field, and generalized fluctuation-dissipation theorem. J. Chem. Phys. 135, 234511 (2011)<\/p>\n<\/li>\n

  210. \n

    Gardiner, C.W.: Handbook of Stochastic Methods for Physics, Chemistry and the Natural Sciences, 3rd edn. Springer, Berlin (2004)<\/p>\n<\/li>\n

  211. \n

    Bialek, W.: Biophysics: Searching for Principles. Princeton University Press, Princeton (2012)<\/p>\n<\/li>\n

  212. \n

    Wu, W., Wang, J.: Landscape framework and global stability for stochastic reaction diffusion and general spatially extended systems with intrinsic fluctuations. J. Phys. Chem. B 117, 12908\u201312934 (2013)<\/p>\n<\/li>\n

  213. \n

    Wu, W., Wang, J.: Potential and flux field landscape theory. I. Global stability and dynamics of spa- tially dependent non-equilibrium systems. J. Chem. Phys. 139, 121920 (2013)<\/p>\n<\/li>\n

  214. \n

    Wu, W., Wang, J.: Potential and flux field landscape theory. II. Non-equilibrium thermodynamics of spatially inhomogeneous stochastic dynamical systems. J. Chem. Phys. 141, 105 (2014)<\/p>\n<\/li>\n

  215. \n

    Zhang, B., Wolynes, P.: Topology, structures, and energy landscapes of human chromosomes. Proc. Natl. Acad. Sci. USA 112, 6062\u20136067 (2015)<\/p>\n<\/li>\n

  216. \n

    Publisher\u2019s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.<\/p>\n<\/li>\n<\/ol>\n


    <\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

    \n
    \n

    \uff08\u53c2\u8003\u6587\u732e\u53ef\u4e0a\u4e0b\u6ed1\u52a8<\/strong>\u67e5\u770b\uff09<\/p>\n<\/section>\n<\/section>\n


    <\/p>\n

    \n


    <\/p>\n

    \n
    \n
    \n
    \n
    \n

    \u56e0\u679c\u6d8c\u73b0\u8bfb\u4e66\u4f1a\u7b2c\u4e8c\u5b63\u62db\u52df\u4e2d<\/strong><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n


    <\/section>\n
    \u8de8\u5c3a\u5ea6\u3001\u8de8\u5c42\u6b21\u7684\u6d8c\u73b0\u662f\u590d\u6742\u7cfb\u7edf\u7814\u7a76\u7684\u5173\u952e\u95ee\u9898\uff0c\u751f\u547d\u8d77\u6e90\u548c\u610f\u8bc6\u8d77\u6e90\u8fd9\u4e24\u5ea7\u4ef0\u4e4b\u5f25\u9ad8\u7684\u5927\u5c71\u662f\u5176\u4ee3\u8868\u3002\u800c\u56e0\u679c\u6d8c\u73b0\u7406\u8bba\u3001\u673a\u5668\u5b66\u4e60\u91cd\u6574\u5316\u6280\u672f\u3001\u81ea\u6307\u52a8\u529b\u5b66\u7b49\u8fd1\u5e74\u6765\u65b0\u5174\u7684\u7406\u8bba\u4e0e\u5de5\u5177\uff0c\u6709\u671b\u7834\u89e3\u590d\u6742\u7cfb\u7edf\u7684\u6d8c\u73b0\u89c4\u5f8b\u3002\u540c\u65f6\uff0c\u65b0\u5174\u7684\u56e0\u679c\u8868\u793a\u5b66\u4e60\u3001\u91cf\u5b50\u56e0\u679c\u7b49\u9886\u57df\u4e5f\u5c06\u4e3a\u56e0\u679c\u6d8c\u73b0\u7814\u7a76\u6ce8\u5165\u65b0\u9c9c\u8840\u6db2\u3002<\/span><\/section>\n

    <\/section>\n
    \u7531\u5317\u4eac\u5e08\u8303\u5927\u5b66\u6559\u6388\u3001\u96c6\u667a\u4ff1\u4e50\u90e8\u521b\u59cb\u4eba\u5f20\u6c5f\u548c\u52a0\u5dde\u5927\u5b66\u5723\u5730\u4e9a\u54e5\u5206\u6821\u52a9\u7406\u6559\u6388\u5c24\u4ea6\u5e84\u7b49\u4eba\u53d1\u8d77\u7684\u300c\u56e0\u679c\u6d8c\u73b0\u300d\u7cfb\u5217\u8bfb\u4e66\u4f1a\u7b2c\u4e8c\u5b63<\/a>\uff0c\u5c06\u7ec4\u7ec7\u5bf9\u672c\u8bdd\u9898\u611f\u5174\u8da3\u7684\u670b\u53cb\uff0c\u6df1\u5165\u7814\u8bfb\u76f8\u5173\u6587\u732e\uff0c\u6fc0\u53d1\u79d1\u7814\u7075\u611f\u3002\u672c\u8bfb\u4e66\u4f1a\u81ea2022\u5e745\u670822\u65e5\u5f00\u59cb\uff0c\u6bcf\u5468\u65e5\u665a19:00\u4e3e\u529e\uff0c\u9884\u8ba1\u6301\u7eed7-8\u5468\u3002\u6b22\u8fce\u611f\u5174\u8da3\u7684\u670b\u53cb\u62a5\u540d\u53c2\u4e0e\u3002<\/span><\/section>\n

    <\/section>\n

    <\/span><\/span><\/a><\/p>\n


    <\/p>\n

    \u672c\u5b63\u8bfb\u4e66\u4f1a\u8be6\u60c5\u4e0e\u62a5\u540d\u65b9\u5f0f\u8bf7\u53c2\u8003\uff1a<\/span><\/strong><\/p>\n

    \u56e0\u679c\u3001\u6d8c\u73b0\u4e0e\u673a\u5668\u5b66\u4e60\uff1a\u56e0\u679c\u6d8c\u73b0\u8bfb\u4e66\u4f1a\u7b2c\u4e8c\u5b63\u542f\u52a8<\/strong><\/a>
    <\/p>\n


    <\/p>\n


    <\/section>\n<\/section>\n
    \n

    \u63a8\u8350\u9605\u8bfb<\/span><\/strong><\/strong><\/p>\n