全文获取类型
收费全文 | 2953篇 |
免费 | 164篇 |
国内免费 | 1篇 |
出版年
2023年 | 4篇 |
2022年 | 12篇 |
2021年 | 35篇 |
2020年 | 15篇 |
2019年 | 24篇 |
2018年 | 34篇 |
2017年 | 47篇 |
2016年 | 57篇 |
2015年 | 91篇 |
2014年 | 107篇 |
2013年 | 268篇 |
2012年 | 170篇 |
2011年 | 154篇 |
2010年 | 117篇 |
2009年 | 110篇 |
2008年 | 175篇 |
2007年 | 199篇 |
2006年 | 223篇 |
2005年 | 189篇 |
2004年 | 196篇 |
2003年 | 170篇 |
2002年 | 138篇 |
2001年 | 36篇 |
2000年 | 31篇 |
1999年 | 46篇 |
1998年 | 30篇 |
1997年 | 29篇 |
1996年 | 29篇 |
1995年 | 29篇 |
1994年 | 34篇 |
1993年 | 25篇 |
1992年 | 32篇 |
1991年 | 26篇 |
1990年 | 27篇 |
1989年 | 15篇 |
1988年 | 26篇 |
1987年 | 20篇 |
1986年 | 15篇 |
1985年 | 18篇 |
1984年 | 17篇 |
1983年 | 9篇 |
1982年 | 15篇 |
1981年 | 14篇 |
1980年 | 7篇 |
1979年 | 10篇 |
1978年 | 9篇 |
1977年 | 6篇 |
1976年 | 9篇 |
1975年 | 6篇 |
1973年 | 4篇 |
排序方式: 共有3118条查询结果,搜索用时 15 毫秒
991.
Shimada H Imaishi K Hirashima T Kitano T Ishikura S Hara A Imamura Y 《Life sciences》2007,80(6):554-558
The stereoselectivity in the reduction of 4-benzoylpyridine (4-BP) was examined in the cytosolic fractions from the heart of 9 vertebrates (pig, rabbit, guinea pig, rat, mouse, chicken, soft-shelled turtle, frog and flounder). 4-BP was stereoselectively reduced to S(-)-alpha-phenyl-4-pyridylmethanol [S(-)-PPOL] in the cytosolic fractions from the heart of pig, rabbit and guinea pig. However, of mammalian heart cytsol tested, only rat heart cytosol had little ability to reduce stereoselectively 4-BP. In an attempt to elucidate this reason, amino acid sequence of rat heart carbonyl reductase (RatHCR) was deduced from the cloned cDNA and compared with that of pig heart carbonyl reductase (PigHCR), which shows a high stereoselectivity in the reduction of 4-BP to S(-)-PPOL. RatHCR showed a high identity with PigHCR in amino acid sequence. Furthermore, recombinant RatHCR was confirmed to reduce stereoselectively 4-BP to S(-)-PPOL with a high optical purity comparable to recombinant PigHCR. It is possible that in the cytosolic fraction from the heart of rat, constitutive reductase other than RatHCR counteracts the stereoselective reduction of 4-BP to S(-)-PPOL, by catalyzing the reduction of 4-BP to the R(+)-enantiomer. 相似文献
992.
Contribution of endogenous glycine and d-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures 总被引:1,自引:0,他引:1
N-methyl-D-aspartate (NMDA) receptors, whose activation requires glycine site stimulation, play crucial roles in various physiological and pathological conditions in the brain. We investigated the regulatory roles of potential endogenous glycine site agonists, glycine and d-serine, in excitotoxic and ischemic cell death in the cerebral cortex. Cytotoxicity of NMDA on rat cerebrocortical slice cultures was potentiated by addition of glycine or d-serine. In contrast, cell death induced by oxygen/glucose deprivation (OGD) was not affected by exogenous glycine or d-serine, although blockade of NMDA receptors by MK-801 abolished cell death. In addition, higher concentrations of 2,7-dichlorokynurenic acid (DCKA), a competitive glycine site antagonist, were required to suppress OGD-induced cell death than those to suppress NMDA cytotoxicity. We also found that OGD triggered a robust increase in extracellular glycine. A glycine transporter blocker ALX 5407 increased the extracellular level of glycine, and the protective effect of DCKA against NMDA cytotoxicity was diminished in the presence of ALX 5407. Sensitivity of NMDA cytotoxicity to DCKA was also diminished by l-serine that increased the extracellular level of d-serine. These results indicate that both glycine and d-serine can act as endogenous ligands for NMDA receptor glycine site in the cerebral cortex, and that endogenous glycine may saturate the glycine site under ischemic conditions. The present findings are important for the interpretation of the mechanisms of NMDA and OGD cytotoxicity. 相似文献
993.
994.
995.
Kume Y Ikeda H Inoue M Tejima K Tomiya T Nishikawa T Watanabe N Ichikawa T Kaneko M Okubo S Yokota H Omata M Fujiwara K Yatomi Y 《FEBS letters》2007,581(8):1631-1634
ADAMTS13 is gaining attention, because its deficiency causes thrombotic thrombocytopenic purpura. Although its regulatory mechanism is not fully understood, we wondered if hepatic stellate cells (HSCs) play a role, because ADAMTS13 mRNA is exclusively expressed in the liver and primarily in HSCs. Plasma ADAMTS13 activity was markedly reduced in dimethylnitrosamine-treated rats, where HSC apoptosis is an essential event, but not in carbon tetrachloride- or thioacetamide-treated rats without HSC apoptosis. Furthermore, plasma ADAMTS13 activity was also reduced in 70% hepatectomized rats, where HSC loss occurs. These results suggest that HSC may be involved in the regulation of plasma ADAMTS13 activity. 相似文献
996.
997.
Toyofuku M Nomura N Fujii T Takaya N Maseda H Sawada I Nakajima T Uchiyama H 《Journal of bacteriology》2007,189(13):4969-4972
Anaerobic growth of Pseudomonas aeruginosa PAO1 was affected by quorum sensing. Deletion of genes that produce N-acyl-l-homoserine lactone signals resulted in an increase in denitrification activity, which was repressed by exogenous signal molecules. The effect of the las quorum-sensing system was dependent on the rhl quorum-sensing system in regulating denitrification. 相似文献
998.
Takano S Kanai F Jazag A Ijichi H Yao J Ogawa H Enomoto N Omata M Nakao A 《Journal of biochemistry》2007,141(3):345-351
Smad4 is a tumour suppressor gene frequently deleted in pancreatic cancer. To investigate the roles of Smad4 deficiency in invasive and matastatic capabilities of pancreatic cancer, we examined the effects of Smad4 deficiency on regulation of the invasion suppressor E-cadherin in pancreatic cancer cell line PANC-1. TGF-beta decreased expression of E-cadherin and beta-catenin proteins at the plasma membrane, increased Snail and Slug mRNA expression, and induced fibroblastoid morphology in PANC-1 cells. These effects of TGF-beta were abrogated in Smad4-knocked-down PANC-1 cells. We also found that TGF-beta-induced down-regulation of E-cadherin expression was partially inhibited in Snail- and Slug-knocked-down PANC-1 cells. Thus, Smad4 mediates down-regulation of E-cadherin induced by TGF-beta in PANC-1 cells, at least in part, through Snail and Slug induction. These results suggest that Smad4 deficiency observed in invasive and metastatic pancreatic cancer might not be linked to the loss of E-cadherin. 相似文献
999.
Hayakawa H Hayakawa M Kume A Tominaga S 《The Journal of biological chemistry》2007,282(36):26369-26380
The ST2 gene produces a soluble secreted form and a transmembrane form, referred to as soluble ST2 and ST2L, respectively. A recent study has reported that interleukin (IL)-33 is a specific ligand of ST2L and induces production of T helper type 2 (Th2) cytokines. Although soluble ST2 is highly produced in sera of asthmatic patients and plays a critical role for production of Th2 cytokines, the function of soluble ST2 in relation to IL-33 signaling remains unclear. Here we show antagonistic effects of soluble ST2 on IL-33 signaling using a murine thymoma EL-4 cells stably expressing ST2L and a murine model of asthma. Soluble ST2 directly bound to IL-33 and suppressed activation of NF-kappaB in EL-4 cells stably expressing ST2L, suggesting that the complex of soluble ST2 and IL-33 fails to bind to ST2L. In a murine model of asthma, pretreatment with soluble ST2 reduced production of IL-4, IL-5, and IL-13 from IL-33-stimulated splenocytes. These results indicate that soluble ST2 acts as a negative regulator of Th2 cytokine production by the IL-33 signaling. Our study provides a molecular mechanism wherein soluble ST2 modulates the biological activity of IL-33 in allergic airway inflammation. 相似文献
1000.
Miyoshi H Perfield JW Souza SC Shen WJ Zhang HH Stancheva ZS Kraemer FB Obin MS Greenberg AS 《The Journal of biological chemistry》2007,282(2):996-1002
Phosphorylation of the lipid droplet-associated protein perilipin A (Peri A) mediates the actions of cyclic AMP-dependent protein kinase A (PKA) to stimulate triglyceride hydrolysis (lipolysis) in adipocytes. Studies addressing how Peri A PKA sites regulate adipocyte lipolysis have relied on non-adipocyte cell models, which express neither adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triglyceride catabolism in mice, nor the "downstream" lipase, hormone-sensitive lipase (HSL). ATGL and HSL are robustly expressed by adipocytes that we generated from murine embryonic fibroblasts of perilipin knock-out mice. Adenoviral expression of Peri A PKA site mutants in these cells reveals that mutation of serine 517 alone is sufficient to abrogate 95% of PKA (forskolin)-stimulated fatty acid (FA) and glycerol release. Moreover, a "phosphomimetic" (aspartic acid) substitution at serine 517 enhances PKA-stimulated FA release over levels obtained with wild type Peri A. Studies with ATGL-and HSL-directed small hairpin RNAs demonstrate that 1) ATGL activity is required for all PKA-stimulated FA and glycerol release in murine embryonic fibroblast adipocytes and 2) all PKA-stimulated FA release in the absence of HSL activity requires serine 517 phosphorylation. These results provide the first demonstration that Peri A regulates ATGL-dependent lipolysis and identify serine 517 as the Peri A PKA site essential for this regulation. The contributions of other PKA sites to PKA-stimulated lipolysis are manifested only in the presence of phosphorylated or phosphomimetic serine 517. Thus, serine 517 is a novel "master regulator" of PKA-stimulated adipocyte lipolysis. 相似文献