首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   5371篇
  免费   416篇
  国内免费   484篇
  2024年   9篇
  2023年   73篇
  2022年   180篇
  2021年   325篇
  2020年   209篇
  2019年   238篇
  2018年   256篇
  2017年   189篇
  2016年   236篇
  2015年   319篇
  2014年   399篇
  2013年   401篇
  2012年   492篇
  2011年   443篇
  2010年   284篇
  2009年   272篇
  2008年   289篇
  2007年   263篇
  2006年   205篇
  2005年   150篇
  2004年   163篇
  2003年   141篇
  2002年   97篇
  2001年   79篇
  2000年   79篇
  1999年   73篇
  1998年   45篇
  1997年   48篇
  1996年   48篇
  1995年   40篇
  1994年   30篇
  1993年   28篇
  1992年   26篇
  1991年   17篇
  1990年   17篇
  1989年   19篇
  1988年   9篇
  1987年   9篇
  1986年   9篇
  1985年   10篇
  1984年   6篇
  1983年   3篇
  1979年   8篇
  1975年   7篇
  1974年   4篇
  1971年   4篇
  1970年   4篇
  1969年   2篇
  1966年   3篇
  1965年   3篇
排序方式: 共有6271条查询结果,搜索用时 15 毫秒
231.
丝状真菌是微生物发酵产品的重要表达体系,其液体深层发酵过程的典型特征是环境因素显著影响菌丝聚集,菌丝聚集影响发酵体系流变特性,进而影响质量传递、热量传递和动量传递,最终影响目标产物生物合成和生产效率。文中首先综述了丝状真菌形态调控的方法和策略,在此基础上针对丝状真菌菌丝生长和聚集过程的两大典型特征——顶端延伸生长和分枝生长,综述和展望了钙信号传导途径和几丁质生物合成途径对调控菌体聚集这一形态的重要意义。  相似文献   
232.
233.
Liao  Xiaodan  Zhao  Zhongpu  Li  Hui  Wu  Bo  Huo  Jiawei  Li  Lei  Li  Xue  Cao  Xinran  Xia  Min  Wang  Chunru  Bai  Chunli 《中国科学:生命科学英文版》2022,65(6):1146-1156

Ulcerative colitis (UC) is a long-term, recurrent inflammatory bowel disease for which no effective cure is yet available in the clinical setting. Repairing the barrier dysfunction of the colon and reducing intestinal inflammation are considered key objectives to cure UC. Here we demonstrate a novel therapeutic strategy based on a C60 fullerene suspension (C60FS) to treat dinitrobenzene sulfonic acid-induced UC in an animal model. C60FS can repair the barrier dysfunction of UC and effectively promote the healing of ulcers; it also manifests better treatment effects compared with mesalazine enema. C60FS can reduce the numbers of basophils in the blood of UC rats and mast cells in the colorectal tissue, thereby effectively alleviating inflammation. The expression of H1R, H4R, and VEGFR2 receptors in colorectal tissues is inhibited by C60FS, and the levels of histamine and prostaglandin in the rat blood are reduced. This work presents a reliable strategy based on fullerene to cure UC and provides a novel guide for UC treatment.

  相似文献   
234.
235.
Zhou  Duanxu  Zhu  Yingmei  Bai  Na  Yang  Le  Xie  Meihua  Yang  Jiangliu  Zhu  Meichen  Zhang  Ke-Qin  Yang  Jinkui 《中国科学:生命科学英文版》2022,65(2):412-425
Science China Life Sciences - Autophagy is an evolutionarily conserved process in eukaryotes, which is regulated by autophagy-related genes (ATGs). Arthrobotrys oligospora is a representative...  相似文献   
236.
Li  Guoli  Su  Bingqian  Fu  Pengfei  Bai  Yilin  Ding  Guangxu  Li  Dahua  Wang  Jiang  Yang  Guoyu  Chu  Beibei 《中国科学:生命科学英文版》2022,65(2):341-361
Science China Life Sciences - Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread. Therefore, the identification of lipids and metabolic...  相似文献   
237.
Science China Life Sciences - Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world. SARS-CoV-2 is an enveloped, plus-stranded RNA virus with a...  相似文献   
238.
D-Serine, a recently identified gliotransmitter, serves as an endogenous coagonist binding to the glycine site of N-methyl-D-aspartate (NMDA) receptors. However, it is not clear whether this native ligand is able to bind to and modulate alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) receptors. In the present study, we showed that D-serine was able to concentration-dependently inhibit kainate-induced AMPA receptor-mediated current in acutely isolated hippocampal neurons. The blocking action of D-serine on AMPA receptors was characterized by a shift in concentration-response curve of kainate-induced current to the right with no change in the maximal response and independent of holding potential in the range of -80 to +60 mV. This is consistent with a model that D-serine is a competitive antagonist on AMPA receptors. In contrast, L-serine did not exert such an inhibitory action. Consistent with this observation, we found that several D-isoforms, but not L-isoforms, of endogenous and exogenous amino acids were able to block AMPA receptors. These results indicate that there is a low affinity and stereo-selective site at the agonist binding pocket of AMPA receptors for these D-amino acids. More importantly, vesicular-released endogenous D-serine from astrocytes could potentially modulate AMPA receptors in synaptic transmission in hippocampus.  相似文献   
239.
The gene sfp1, which encodes a predicted serine proteinase designated SFP1, was isolated by the screening of a gene library of the feather-degrading strain Streptomyces fradiae var.k11. The open reading frame of sfp1 encodes a protein of 454 amino acids with a calculated molecular mass of 46.19 kDa. Sequence analysis reveals that SFP1 possesses a typical pre-pro-mature organization that consists of a signal sequence, an N-terminal propeptide region, and a mature proteinase domain. The pre-enzyme of SFP1 was expressed in Escherichia coli and consequently purified. The 25.6 kDa fraction with protease activity separated by gel filtration chromatography indicated that the mature enzyme of SFP1 was formed by autolysis of the propeptide after its expression. The purified SFP1 is active under a broad range of pH and temperature. SFP1 has pH and temperature optima of pH 8.5 and 65 degrees C for its caseinolytic activity and pH 9 and 62 degrees C for its keratinolytic activity. SFP1 was sharply inhibited by the serine proteinase inhibitor phenylmethyl sulfonyl fluoride and exhibited a good stability to solvents, detergents, and salts. Comparison of the protease activity of SFP1 with other commercial proteases indicates that SFP1 has a considerable caseinolytic and keratinolytic activity as does proteinase K.  相似文献   
240.
Bai L  Merchant JL 《FEBS letters》2007,581(30):5904-5910
A thorough understanding of histone acetyltransferase CBP/p300-mediated regulation of gene expression and cell growth is essential to identify mechanisms relevant to the development of histone deacetylase (HDAC) inhibitor-based preventive and therapeutic strategies. We found that knockdown of CBP/p300 interacting coactivator with glutamic acid/aspartic acid-rich tail 2 (CITED2) increased colon cancer cell invasiveness in vitro. Gene expression profiling revealed that CITED2 knockdown induced matrix metalloproteinase-13 (MMP-13) gene expression in colon cancer cells. Butyrate, a naturally occurring HDAC inhibitor, induced CITED2 expression and downregulated MMP-13 expression in RKO cells. Additionally, ectopic expression of CITED2 arrested RKO cell growth. Thus, CITED2 regulates colon cancer invasion and might be a target for HDAC inhibitor-based intervention of colon cancer.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号