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   2984篇
  免费   157篇
  2022年   19篇
  2021年   30篇
  2020年   19篇
  2019年   32篇
  2018年   44篇
  2017年   45篇
  2016年   80篇
  2015年   111篇
  2014年   112篇
  2013年   212篇
  2012年   218篇
  2011年   195篇
  2010年   120篇
  2009年   117篇
  2008年   182篇
  2007年   184篇
  2006年   182篇
  2005年   163篇
  2004年   152篇
  2003年   135篇
  2002年   128篇
  2001年   27篇
  2000年   19篇
  1999年   29篇
  1998年   26篇
  1997年   32篇
  1996年   27篇
  1995年   27篇
  1994年   23篇
  1993年   29篇
  1992年   27篇
  1991年   25篇
  1990年   27篇
  1989年   17篇
  1988年   23篇
  1987年   20篇
  1986年   17篇
  1985年   17篇
  1984年   29篇
  1983年   25篇
  1982年   19篇
  1981年   16篇
  1980年   21篇
  1979年   21篇
  1978年   21篇
  1977年   11篇
  1976年   10篇
  1975年   13篇
  1974年   9篇
  1973年   12篇
排序方式: 共有3141条查询结果,搜索用时 812 毫秒
111.
112.
In the present study, a small set of reversible or irreversible 4-anilinoquinazoline EGFR inhibitors was tested in A549 cells at early (1 h) and late (8 h) time points after inhibitor removal from culture medium. A combination of assays was employed to explain the observed long-lasting inhibition of EGFR autophosphorylation. We found that EGFR inhibition at 8 h can be due, besides to the covalent interaction of the inhibitor with Cys797, as for PD168393 (2) and its prodrug 4, to the intracellular accumulation of non-covalent inhibitors by means of an active cell uptake, as for 5 and 6. Compounds 5–6 showed similar potency and duration of inhibition of EGFR autophosphorylation as the covalent inhibitor 2, while being devoid of reactive groups forming covalent bonds with protein thiols.  相似文献   
113.
Mutations in leucine-rich repeat kinase-2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). The most frequent kinase-enhancing mutation is the G2019S residing in the kinase activation domain. This opens up a promising therapeutic avenue for drug discovery targeting the kinase activity of LRRK2 in PD. Several LRRK2 inhibitors have been reported to date. Here, we report a selective, brain penetrant LRRK2 inhibitor and demonstrate by a competition pulldown assay in vivo target engagement in mice.  相似文献   
114.
115.
Detecting bottlenecks is a common task in molecular ecology. While several bottleneck detection methods exist, evaluations of their power have focused only on severe bottlenecks (e.g. to Ne ~10). As a component of a recent review, Peery et al. ( 2012 ) analysed the power of two approaches, the M‐ratio and heterozygote excess tests, to detect moderate bottlenecks (e.g. to Ne ~100), which is realistic for many conservation situations. In this Comment, we address three important points relevant to but not considered in Peery et al. Under moderate bottleneck scenarios, we test the (i) relative advantage of sampling more markers vs. more individuals, (ii) potential power to detect the bottleneck when utilizing dozens of microsatellites (a realistic possibility for contemporary studies) and (iii) reduction in power when postbottleneck recovery has occurred. For the realistic situations examined, we show that (i) doubling the number of loci shows equal or better power than tripling the number of individuals, (ii) increasing the number of markers (up to 100) results in continued additive gains in power, and (iii) recovery after a moderate amount of time or gradual change in size reduces power, by up to one‐half. Our results provide a practical supplement to Peery et al. and encourage the continued use of bottleneck detection methods in the genomic age, but also emphasize that the power under different sampling schemes should be estimated, using simulation modelling, as a routine component of molecular ecology studies.  相似文献   
116.
117.
118.
The Etruscan culture is documented in Etruria, Central Italy, from the 8th to the 1st century BC. For more than 2,000 years there has been disagreement on the Etruscans’ biological origins, whether local or in Anatolia. Genetic affinities with both Tuscan and Anatolian populations have been reported, but so far all attempts have failed to fit the Etruscans’ and modern populations in the same genealogy. We extracted and typed the hypervariable region of mitochondrial DNA of 14 individuals buried in two Etruscan necropoleis, analyzing them along with other Etruscan and Medieval samples, and 4,910 contemporary individuals from the Mediterranean basin. Comparing ancient (30 Etruscans, 27 Medieval individuals) and modern DNA sequences (370 Tuscans), with the results of millions of computer simulations, we show that the Etruscans can be considered ancestral, with a high degree of confidence, to the current inhabitants of Casentino and Volterra, but not to the general contemporary population of the former Etruscan homeland. By further considering two Anatolian samples (35 and 123 individuals) we could estimate that the genetic links between Tuscany and Anatolia date back to at least 5,000 years ago, strongly suggesting that the Etruscan culture developed locally, and not as an immediate consequence of immigration from the Eastern Mediterranean shores.  相似文献   
119.
120.
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