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   2726篇
  免费   18篇
  国内免费   61篇
  2805篇
  2023年   2篇
  2022年   2篇
  2021年   12篇
  2020年   8篇
  2019年   17篇
  2018年   19篇
  2017年   13篇
  2016年   7篇
  2015年   84篇
  2014年   260篇
  2013年   255篇
  2012年   377篇
  2011年   492篇
  2010年   426篇
  2009年   47篇
  2008年   42篇
  2007年   48篇
  2006年   43篇
  2005年   44篇
  2004年   35篇
  2003年   39篇
  2002年   22篇
  2001年   22篇
  2000年   25篇
  1999年   28篇
  1998年   32篇
  1997年   27篇
  1996年   28篇
  1995年   30篇
  1994年   25篇
  1993年   15篇
  1992年   15篇
  1991年   22篇
  1990年   20篇
  1989年   21篇
  1988年   26篇
  1987年   14篇
  1986年   23篇
  1985年   20篇
  1984年   9篇
  1983年   8篇
  1982年   15篇
  1981年   17篇
  1980年   22篇
  1979年   11篇
  1978年   8篇
  1977年   12篇
  1976年   11篇
  1974年   3篇
  1973年   1篇
排序方式: 共有2805条查询结果,搜索用时 0 毫秒
101.
102.
Dermorphin and its Hyp6 analogue are opiate-like heptapeptides originally discovered in frog skin and characterized by the presence of a D-Ala2 residue in their sequence. They were assayed for their capacity to compete with [3H]Leu-enkephalin for binding to opioid receptors in membranes of neuroblastoma x glioma hybrid cells. In the presence of 7 nM-[3H]Leu-enkephalin, the concentrations at which they caused 50% inhibition of [3H]enkephalin binding (IC50 values) are 0.1 micro M and 0.3 micro M, respectively. In contrast, the synthetic L-Ala2-dermorphin shows very low affinity for the opioid receptors. In addition, like other opioid peptides, dermorphin and hyp6-dermorphin inhibit the elevation by prostaglandin E1 (PGE1) of the level of adenosine 3':5'-cyclic monophosphate (cyclic AMP) (IC50 values 0.2 micro M and 0.4 micro M, respectively). The inhibition is prevented by the opiate antagonist naloxone, L-Ala2-dermorphin is at least three orders of magnitude less potent in inhibiting the PGE1-evoked increase in the level of cyclic AMP. The results show that peptides with an amino acid sequence quite different from that of the enkephalins can bind to opioid receptors of the hybrid cells.  相似文献   
103.
A growing body of evidence points toward activated fibroblasts, also known as myofibroblasts, as one of the leading mediators in several major human pathologies including proliferative fibrotic disorders, invasive tumor growth, rheumatoid arthritis, and atherosclerosis. Niemann-Pick Type C2 (NPC2) protein has been recently identified as a product of the second gene in NPC disease. It encodes ubiquitous, highly conserved, secretory protein with the poorly defined function. Here we show that NPC2 deficiency in human fibroblasts confers their activation. The activation phenomenon was not limited to fibroblasts as it was also observed in aortic smooth muscle cells upon silencing NPC2 gene by siRNA. More importantly, activated synovial fibroblasts isolated from patients with rheumatoid arthritis were also identified as NPC2-deficient at both the NPC2 mRNA and protein levels. The molecular mechanism responsible for activation of NPC2-null cells was shown to be a sustained phosphorylation of ERK 1/2 mitogen-activated protein kinase (MAPK), which fulfills both the sufficient and necessary fibroblast activation criteria. All of these findings highlight a novel mechanism where NPC2 by negatively regulating ERK 1/2 MAPK phosphorylation may efficiently suppress development of maladaptive tissue remodeling and inflammation.  相似文献   
104.
105.
The -isopropylmalate synthase of the chemolithoautotrophic Alcaligenes eutrophus H16 is apparently a soluble enzyme but is strongly adsorbed to cell particles in ruptured cell suspensions. This was not observed with -acetohydroxy acid synthase or threonine deaminase. The formation of these regulatory enzymes of the branched chain amino acid biosynthesis pathway generally decreased with decreased growth rates. The addition of 5 mM valine plus isoleucine with and without 5 mM threonine caused a 6.6- and a 4-fold increase, respectively, in the formation of active -isopropylmalate synthase, but caused a strong decrease in the -actohydroxy acid synthase. The level of active -isopropylmalate synthase is apparently regulated by the level of leucine; whereas, the level of the -acetohydroxy acid synthase and threonine deaminase is influenced by the presence of several amino acids. A catabolic threonine deaminase was not encountered.Abbreviations IRS -Isopropylamalate - AHA -acetohydroxy acid - TDA throninedeaminase This paper is dedicated to Professor H. G. Schlegel, University Göttingen, on the occasion of his 60th birthday. I am grateful to a great teacher and scientist, who in his unique way stimulated enthusiasm and fascination in microbiology in his students throughout the years  相似文献   
106.
107.
周志华  金效华 《生物多样性》2021,29(12):1583-1590
中国是全球生物多样性最丰富的国家之一.最近40年,中国的植物多样性保护取得了巨大成就,实施了多项政策和法律,尤其是《野生植物保护条例》和《国家重点保护野生植物名录》先后颁布,奠定了中国植物保护的法律和政策框架,就地保护和迁地保护网络基本形成.但与生态文明建设的要求相比,野生植物保护依然存在许多不足.本文系统回顾了中国野...  相似文献   
108.
Crescentic glomerulonephritis (Crgn) is a complex disease where the initial insult is often the glomerular deposition of antibodies against intrinsic or deposited antigens in the glomerulus. The role of Fc receptors in the induction and progression of Crgn is increasingly recognized, and our previous studies have shown that copy number variation in Fcgr3 partially explains the genetic susceptibility of the Wistar-Kyoto (WKY) rat to nephrotoxic nephritis, a rat model of Crgn. The Fcgr3-related sequence (Fcgr3-rs) is a novel rat-specific Fc receptor with a cytoplasmic domain 6 amino acids longer than its paralogue, Fcgr3. The Fcgr3-rs gene is deleted from the WKY rat genome, and this deletion is associated with enhanced macrophage activity in this strain. Here, we investigated the mechanism by which the deletion of Fcgr3-rs in the WKY strain leads to increased macrophage activation. By lentivirus-mediated gene delivery, we generated stably transduced U937 cells expressing either Fcgr3-rs or Fcgr3. In these cells, which lack endogenous Fcgr3 receptors, we show that Fcgr3-rs interacts with the common Fc-γ chain but that Fc receptor-mediated phagocytosis and signaling are defective. Furthermore, in primary macrophages, expression of Fcgr3-rs inhibits Fc receptor-mediated functions, because WKY bone marrow-derived macrophages transduced with Fcgr3-rs had significantly reduced phagocytic activity. This inhibitory effect on phagocytosis was mediated by the novel cytoplasmic domain of Fcgr3-rs. These results suggest that Fcgr3-rs may act to inhibit Fcgr3-mediated signaling and phagocytosis and could be considered as a novel mechanism in the modulation of Fc receptor-mediated cell activation in autoimmune diseases.  相似文献   
109.
110.
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