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   684篇
  国内免费   1篇
  完全免费   60篇
  2019年   2篇
  2018年   9篇
  2017年   7篇
  2016年   5篇
  2015年   4篇
  2014年   13篇
  2013年   14篇
  2012年   39篇
  2011年   33篇
  2010年   13篇
  2009年   16篇
  2008年   45篇
  2007年   46篇
  2006年   39篇
  2005年   42篇
  2004年   41篇
  2003年   46篇
  2002年   37篇
  2001年   35篇
  2000年   30篇
  1999年   31篇
  1998年   24篇
  1997年   4篇
  1996年   6篇
  1995年   6篇
  1994年   7篇
  1993年   3篇
  1992年   22篇
  1991年   23篇
  1990年   13篇
  1989年   8篇
  1988年   16篇
  1987年   8篇
  1986年   8篇
  1985年   10篇
  1984年   3篇
  1983年   6篇
  1982年   3篇
  1981年   1篇
  1980年   2篇
  1979年   4篇
  1978年   1篇
  1976年   1篇
  1975年   3篇
  1974年   2篇
  1972年   3篇
  1970年   4篇
  1968年   4篇
  1967年   1篇
  1962年   1篇
  1960年   1篇
排序方式: 共有745条查询结果,搜索用时 250 毫秒
1.
2.
To examine the function of the amino-terminal presequence of rat peroxisomal 3-ketoacyl-CoA thiolase precursor, fusion proteins of various amino-terminal regions of the precursor with non-peroxisomal enzymes were expressed in cultured mammalian cells. On immunofluorescence microscopy, all constructs carrying the presequence part exhibited punctate patterns of distribution, identical with that of catalase, a peroxisomal marker. Proteins lacking all or a part of the prepiece were found in the cytosol. These results indicate that the presequence of the thiolase has sufficient information for peroxisomal targeting.  相似文献
3.
Enhanced expression of adenovirus transforming proteins.   总被引:41,自引:25,他引:16       下载免费PDF全文
4.
5.
Enzymatic control of pigmentation in mammals.   总被引:34,自引:0,他引:34  
Visible pigmentation in mammals results from the synthesis and distribution of melanin in the skin, hair bulbs, and eyes. The melanins are produced in melanocytes and can be of two basic types: eumelanins, which are brown or black, and phaseomelanins, which are red or yellow. In mammals typically there are mixtures of both types. The most essential enzyme in this melanin biosynthetic pathway is tyrosinase and it is the only enzyme absolutely required for melanin production. However, recent studies have shown that mammalian melanogenesis is not regulated solely by tyrosinase at the enzymatic level, and have identified additional melanogenic factors that can modulate pigmentation in either a positive or negative fashion. In addition, other pigment-specific genes that are related to tyrosinase have been cloned which encode proteins that apparently work together at the catalytic level to specify the quantity and quality of the melanins synthesized. Future research should provide a greater understanding of the enzymatic interactions, processing, and tissue specificity that are important to pigmentation in mammals.  相似文献
6.
Current concepts in the pathogenesis of alcoholic liver injury.   总被引:32,自引:0,他引:32  
H Tsukamoto  S C Lu 《The FASEB journal》2001,15(8):1335-1349
Alcoholic liver disease (ALD) develops as a consequence of priming and sensitizing mechanisms rendered by cross-interactions of primary mechanistic factors and secondary risk factors. This concept, albeit not novel, is becoming widely accepted by the field, and more research is directed toward identifying and characterizing the interfaces of the cross-interactions to help understand individual predisposition to the disease. Another pivotal development is the beginning of cell type-specific research to elucidate specific contributions not only of hepatocytes, but also of hepatic macrophages, liver-associated lymphocytes, sinusoidal endothelial cells, and hepatic stellate cells to sensitizing and priming mechanisms. In particular, the critical role of hepatic macrophages has been highlighted and the priming mechanisms concerning this paracrine effect have been proposed. Glutathione depletion in hepatocyte mitochondria is considered the most important sensitizing mechanism. One of the contributing factors is decreased methionine metabolism. Remaining key questions include how altered methionine metabolism contribute to the pathogenesis of ALD; how cross-talk among nonparenchymal liver cells or between nonparenchymal cells and hepatocytes leads to ALD; how dysfunctional mitochondria determine the type of cell death in ALD; and what secondary factors are critical for the development of advanced ALD such as alcoholic hepatitis and cirrhosis.  相似文献
7.
8.
RTP/Drg1/Cap43/rit42/TDD5/Ndr1/NDRG1 (referred to as NDRG1 hereafter) is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. Recently, the mutation of this gene was reported to be causative for hereditary motor and sensory neuropathy-Lom. Here, we cloned two human cDNAs encoding NDRG3 and NDRG4, which are homologous to NDRG1. These two genes, together with NDRG1 and a previously deposited cDNA (designated NDRG2), constitute the NDRG gene family. The four members share 57-65% amino acid identity. NDRG4 was further characterized because its mRNA expression was quite specific in brain and heart, in contrast to the relatively ubiquitous expression of the other three members. NDRG4 mRNA consists of three isoforms, NDRG4-B, NDRG4-B(var), and NDRG4-H. Northern and Western blot analyses showed that NDRG4-B was expressed only in the brain, whereas NDRG4-H was expressed in both brain and heart. NDRG4-B(var) was a minor product. NDRG4 expression was more abundant in adult than fetal brain and heart and was markedly decreased in the Alzheimer's diseased brain. In situ hybridization showed that NDRG4 was localized in neurons of the brain and spinal cord. The NDRG4 gene contains 17 exons. mRNA expression of the three NDRG4 isoforms is regulated by alternative splicing and possibly by alternative promoter usage. The finely tuned expression of the NDRG gene family members suggests that they have different specific functions.  相似文献
9.
Macrophage production of fibronectin, a chemoattractant for fibroblasts   总被引:22,自引:0,他引:22  
Activation of macrophages results in the production of numerous enzymes and effector molecules. One of these monokines released by macrophages can cause directed migration of connective tissue fibroblasts in vitro. Production of this macrophage-derived chemotactic factor for fibroblasts requires activation of the macrophages either in vivo or in vitro and de novo protein synthesis. The chemotactic activity in the macrophage supernatants could be removed by a fibronectin-specific affinity column and was inhibited in the presence of antibodies to fibronectin. Furthermore, chemotactic activity in the depleted macrophage supernatants could be restored by the addition of exogenous fibronectin. Fibronectin was identified in activated macrophage supernatants by an enzyme-linked immunoassay for fibronectin. From these findings it was concluded that activated macrophages release a chemoattractant for fibroblasts and that the primary chemoattractant molecule is fibronectin. The production of fibronectin by activated macrophages may thus serve as an inflammatory mediator that in addition to its other functions can recruit fibroblasts to an area of damaged tissue, where they can proliferate and form the scar tissue necessary for tissue repair. Furthermore, in chronic inflammation, the prolonged activation of macrophages may be related to the extensive fibroblast infiltration and fibrosis that can accompany these lesions.  相似文献
10.
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