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   440篇
  免费   59篇
  国内免费   6篇
  2023年   4篇
  2022年   6篇
  2021年   14篇
  2020年   9篇
  2019年   11篇
  2018年   13篇
  2017年   7篇
  2016年   14篇
  2015年   20篇
  2014年   19篇
  2013年   30篇
  2012年   34篇
  2011年   37篇
  2010年   29篇
  2009年   28篇
  2008年   29篇
  2007年   25篇
  2006年   16篇
  2005年   16篇
  2004年   15篇
  2003年   14篇
  2002年   9篇
  2001年   9篇
  2000年   9篇
  1999年   4篇
  1998年   2篇
  1995年   1篇
  1994年   2篇
  1993年   3篇
  1992年   4篇
  1991年   4篇
  1990年   7篇
  1989年   4篇
  1988年   2篇
  1987年   3篇
  1986年   5篇
  1985年   6篇
  1984年   4篇
  1983年   4篇
  1982年   6篇
  1981年   5篇
  1979年   3篇
  1978年   4篇
  1977年   3篇
  1976年   3篇
  1975年   1篇
  1972年   3篇
  1971年   2篇
  1968年   1篇
  1959年   1篇
排序方式: 共有505条查询结果,搜索用时 15 毫秒
441.
The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors bearing a butynyloxy P1' group was explored. In particular, compound 5k has excellent in vitro potency against TACE enzyme and in cells, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model.  相似文献   
442.
A mass was identified on the left caudal region of the abdomen in a 13-year-old bonnet monkey (Macaca radiata). The mass was excised and diagnosed as granulosa theca cell tumor accompanied with luteoma based on the microscopic findings. Morphologically it appeared pink, round, firm multilobulated measured approximately 5 x 3 x 2.5 cm in dimension. Histologically the luteoma composed of polyhedral cells with pale strained vacuolated cytoplasm, centrally located nuclei with distinct cytoplasmic borders. Granulosa theca cell tumor appeared as densely packed spindle shaped fusiform cells arranged in interlacing bundles and whorled pattern with neoplastic cells appearing irregular shaped solid sheets. The concomitant development of granulosa theca cell tumor with luteoma in a single ovary is very rare and is the first reported case in a bonnet macaque to our knowledge.  相似文献   
443.
Fu X  Chan TM  Tann CH  Thiruvengadam TK 《Steroids》2002,67(7):549-554
Two new C-nor/D-homo corticosteroids were isolated from the filtrate of the triene carbonate intermediate during the production of betamethasone. Their structures were elucidated based on NMR spectroscopic studies and mass spectral analyses. The mechanism of formation of each of these two steroids was postulated as a Wagner-Meerwein rearrangement of the corresponding 12beta-hydroxy steroid. The new 12beta-hydroxy corticosteroid was also isolated from the fermentation process of betamethasone synthesis. Its structure was identified via NMR and mass spectroscopic studies. Treatment of the new 12beta-hydroxy corticoid with PCl(5) at low temperature provided two C-nor/D-homo compounds in a ratio of 1:1. Conversion of 12beta-hydroxy corticoid into a corresponding 12beta-mesylate followed by heating in HOAc to 110 degrees C in the presence of NaOAc produced a mixture of the rearranged products in a 1:4 ratio.  相似文献   
444.
Yang SL  Xie LF  Mao HZ  Puah CS  Yang WC  Jiang L  Sundaresan V  Ye D 《The Plant cell》2003,15(12):2792-2804
In flowering plants, pollen formation depends on the differentiation and interaction of two cell types in the anther: the reproductive cells, called microsporocytes, and somatic cells that form the tapetum. The microsporocytes generate microspores, whereas the tapetal cells support the development of microspores into mature pollen grains. Despite their importance to plant reproduction, little is known about the underlying genetic mechanisms that regulate the differentiation and interaction of these highly specialized cells in the anther. Here, we report the identification and characterization of a novel tapetum determinant1 (TPD1) gene that is required for the specialization of tapetal cells in the Arabidopsis anther. Analysis of the male-sterile mutant, tpd1, showed that functional interruption of TPD1 caused the precursors of tapetal cells to differentiate and develop into microsporocytes instead of tapetum. As a results, extra microsporocytes were formed and tapetum was absent in developing tpd1 anthers. Molecular cloning of TPD1 revealed that it encodes a small protein of 176 amino acids. In addition, tpd1 was phenotypically similar to excess microsporocytes1/extra sporogenous cells (ems1/exs) single and tpd1 ems1/exs double mutants. These data suggest that the TPD1 product plays an important role in the differentiation of tapetal cells, possibly in coordination with the EMS1/EXS gene product, a Leu-rich repeat receptor protein kinase.  相似文献   
445.
446.
The protective effect of L-arginine and L-lysine on lysosomal enzymes and membrane bound ATPases was examined on isoproterenol induced myocardial infarction in rats. Lysosomal enzymes play an important role in the inflammatory process. The rats given isoproterenol (150 mg kg–1 daily) intraperitoneally for 2 days showed significant changes in the marker enzymes, lysosomal enzymes and membrane bound phosphatases. Histopathological studies also confirmed the induction of myocardial infarction in isoproterenol administered rats. Prior oral treatment with L-arginine (250 mg kg–1 daily) and L-lysine (5 mg kg–1 daily) for 5 days significantly prevented these alterations and restored the enzyme activities to near normal. These findings demonstrate the protective effect of L-arginine and L-lysine in combination against isoproterenol induced cardiac damage.  相似文献   
447.
Glutamate, a major excitatory amino acid neurotransmitter is also an endogenous excitotoxin. The present study examined the prolonged and delayed effects of glutamate excitotoxicity on mitochondrial lipid peroxidation and antioxidant parameters in different brain regions, namely, cerebral hemisphere, cerebellum, brain stem and diencephalon. Wistar rats (male) were exposed to monosodium glutamate (MSG) (4 mg × g body wt–1, i.p.) for 6 consecutive days and sacrificed on 30th and 45th day after last MSG dose. MSG treatment markedly decreased the mitochondrial manganese superoxide-dismutase (Mn-SOD), catalase and reduced glutathione (GSH) content, and increased the lipid peroxidation (LPx), uric acid and glutathione peroxidase (GPx) activity. These results indicate that oxidative stress produced by glutamate in vulnerable brain regions may persist for longer periods and mitochondrial function impairment is an important mechanism of excitatory amino acid mediated neurotoxicity in chronic neurodegeneration.  相似文献   
448.
It is well established that leukocyte chemotactic receptors, a subset of G protein-coupled receptors, undergo endocytosis after stimulation by ligand. However, the significance of this phenomenon to cell motility and other important leukocyte functions induced by chemoattractants has not been clearly defined. Here we show that in primary human neutrophils, the threshold levels of agonist required for endocytosis of the chemotactic receptors CXCR1 and CXCR2 were approximately 10-fold or higher than those needed for maximal chemotactic and calcium flux responses. Moreover, when stimulated by agonists at concentrations that are high enough for chemotaxis but too low for receptor endocytosis, neutrophil CXCR1 and CXCR2 could be reactivated in response to repeated application of the same agonist. Both receptors were excluded from Triton X-100-insoluble lipid rafts, and at high agonist concentrations were rapidly endocytosed by a clathrin/rab5/dynamin-dependent pathway. These data support the conclusion that neutrophil migration in response to CXCR1 or CXCR2 agonists is not dependent on endocytosis of CXCR1 or CXCR2. Rather than being integral to the process of cell migration, receptor endocytosis may be a terminal stop signal when cells reach the focus of inflammation where the chemoattractant concentrations are the highest.  相似文献   
449.
450.
A significant fraction (approximately 17%) of Arabidopsis genes are members of tandemly repeated families and pose a particular challenge for functional studies. We have used the Ac-Ds transposition system to generate single- and double-knockout mutants of two tandemly duplicated cytochrome P450 genes, SPS/BUS/CYP79F1 and CYP79F2. We have previously described the Arabidopsis supershoot mutants in CYP79F1 that exhibit massive overproliferation of shoots. Here we use a cytokinin-responsive reporter ARR5::uidA and an auxin-responsive reporter DR5::uidA in the sps/cyp79F1 mutant to show that increased levels of cytokinin, but not auxin, correlate well with the expression pattern of the SPS/CYP79F1 gene, supporting the involvement of this gene in cytokinin homeostasis. Further, we isolated Ds gene trap insertions in the CYP79F2 gene, and find these mutants to be defective mainly in the root system, consistent with a root-specific expression pattern. Finally, we generated double mutants in CYP79F1 and CYP79F2 using secondary transpositions, and demonstrate that the phenotypes are additive. Previous biochemical studies have suggested partially redundant functions for SPS/CYP79F1 and CYP79F2 in aliphatic glucosinolate synthesis. Our analysis shows that aliphatic glucosinolate biosynthesis is completely abolished in the double-knockout plants, providing genetic proof for the proposed biochemical functions of these genes. This study also provides further demonstration of how gluconisolate biosynthesis, regarded as secondary metabolism, is intricately linked with hormone homeostatis and hence with plant growth and development.  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