全文获取类型
收费全文 | 3521篇 |
免费 | 248篇 |
国内免费 | 3篇 |
出版年
2023年 | 20篇 |
2022年 | 35篇 |
2021年 | 88篇 |
2020年 | 71篇 |
2019年 | 83篇 |
2018年 | 111篇 |
2017年 | 99篇 |
2016年 | 151篇 |
2015年 | 222篇 |
2014年 | 230篇 |
2013年 | 303篇 |
2012年 | 330篇 |
2011年 | 300篇 |
2010年 | 195篇 |
2009年 | 175篇 |
2008年 | 245篇 |
2007年 | 213篇 |
2006年 | 169篇 |
2005年 | 151篇 |
2004年 | 145篇 |
2003年 | 101篇 |
2002年 | 74篇 |
2001年 | 63篇 |
2000年 | 39篇 |
1999年 | 34篇 |
1998年 | 13篇 |
1997年 | 15篇 |
1996年 | 11篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 7篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1984年 | 8篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 2篇 |
1968年 | 1篇 |
1960年 | 1篇 |
1954年 | 3篇 |
排序方式: 共有3772条查询结果,搜索用时 15 毫秒
171.
We have examined expression of the lambdacI operon in single cells via a rex Colon, two colons gfp substitution. Although average fluorescence agreed with expectations for expression of lambda-repressor, fluorescence fluctuated greatly from cell-to-cell. Fluctuations in repressor concentration are not predicted by previous models and are tolerated in part by a regulatory response to DNA damage. 相似文献
172.
173.
174.
Miyakoshi A Yoon WK Jee Y Matsumoto Y 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):6371-6378
Like Lewis rats, DA rats are an experimental autoimmune encephalomyelitis (EAE)-susceptible strain and develop severe EAE upon immunization with myelin basic protein (MBP). However, there are several differences between the two strains. In the present study we induced acute EAE in DA rats by immunization with MBP and MBP peptides and examined the Ag specificity and TCR repertoire of encephalitogenic T cells. It was found that although immunization with MBP and a peptide corresponding to its 62-75 sequence (MBP(62-75)) induced clinical EAE, the responses of lymph node T cells isolated from MBP-immunized rats to MBP(62-75) was marginal, indicating that this peptide contains major encephalitogenic, but not immunodominant, epitopes. The TCR analysis by CDR3 spectratyping of spinal cord T cells revealed that Vbeta10 and Vbeta15 spectratype expansion was always found in MBP(62-75)-immunized symptomatic rats. On the basis of these findings, we examined the encephalitogenicity of Vbeta10- and Vbeta15-positive T cells. First, the adoptive transfer experiments revealed that Vbeta10-positive T line cells derived from MBP(62-75)-immunized rats induced clinical EAE in recipients. Second, administration of DNA vaccines encoding Vbeta10 and Vbeta15, alone or in combination, ameliorated MBP(62-75)-induced EAE. Collectively, it was strongly suggested that Vbeta10- and Vbeta15-positive T cells are encephalitogenic. Analyses of the Ag specificity and T cell repertoire of pathogenic T cells performed in this study provide useful information for designing specific immunotherapies against autoimmune diseases. 相似文献
175.
Oxidative stress induces nuclear loss of DNA repair proteins Ku70 and Ku80 and apoptosis in pancreatic acinar AR42J cells 总被引:6,自引:0,他引:6
Cell death linked to oxidative DNA damage has been implicated in acute pancreatitis. The severe DNA damage, which is beyond the capacity of the DNA repair proteins, triggers apoptosis. It has been hypothesized that oxidative stress may induce a decrease in the Ku70 and Ku80 levels and apoptosis in pancreatic acinar cells. In this study, it was found that oxidative stress caused by glucose oxidase (GO) acting on beta-d-glucose, glucose/glucose oxidase (G/GO), induced slight changes in cytoplasmic Ku70 and Ku80 but drastically induced a decrease in nuclear Ku70 and Ku80 both time- and concentration-dependently in AR42J cells. G/GO induced apoptosis determined by poly(ADP-ribose) polymerase cleavage, an increase in expression of p53 and Bax, and a decrease in Bcl-2 expression. G/GO-induced apoptosis was in parallel with the loss of nuclear Ku proteins in AR42J cells. Caspase-3 inhibitor prevented G/GO-induced nuclear Ku loss and cell death. G/GO did not induce apoptosis in the cells transfected with either the Ku70 or Ku80 expression gene but increased apoptosis in those transfected with the Ku dominant negative mutant. Pulse and pulse-chase results show that G/GO induced Ku70 and Ku80 syntheses, even though Ku70 and Ku80 were degraded both in cytoplasm and nucleus. G/GO-induced decrease in Ku binding to importin alpha and importin beta reflects possible modification of nuclear import of Ku proteins. The importin beta level was not changed by G/GO. These results demonstrate that nuclear decrease in Ku70 and Ku80 may result from the decrease in Ku binding to nuclear transporter importins and the degradation of Ku proteins. The nuclear loss of Ku proteins may underlie the mechanism of apoptosis in pancreatic acinar cells after oxidative stress. 相似文献
176.
Ethanol impairs insulin-stimulated neuronal survival in the developing brain: role of PTEN phosphatase 总被引:1,自引:0,他引:1
Xu J Yeon JE Chang H Tison G Chen GJ Wands J de la Monte S 《The Journal of biological chemistry》2003,278(29):26929-26937
Gestational exposure to ethanol causes fetal alcohol syndrome, which is associated with cerebellar hypoplasia. Previous in vitro studies demonstrated ethanol-impaired neuronal survival with reduced signaling through the insulin receptor (IRbeta). We examined insulin signaling in an experimental rat model of chronic gestational exposure to ethanol in which the pups exhibited striking cerebellar hypoplasia with increased apoptosis. Immunoprecipitation and Western blot analyses detected reduced levels of tyrosyl-phosphorylated IRbeta, tyrosyl-phosphorylated insulin receptor substrate-1 (IRS-1), and p85-associated IRS-1 but no alterations in IRbeta, IRS-1, or p85 protein expression in cerebellar tissue from ethanol-exposed pups. In addition, ethanol exposure significantly reduced the levels of total phosphoinositol 3-kinase, Akt kinase, phospho-BAD (inactive), and glyceraldehyde-3-phosphate dehydrogenase and increased the levels of glycogen synthase kinase-3 activity, activated BAD, phosphatase and tensin homolog deleted in chromosome 10 (PTEN) protein, and PTEN phosphatase activity in cerebellar tissue. Cerebellar neurons isolated from ethanol-exposed pups had reduced levels of insulin-stimulated phosphoinositol 3-kinase and Akt kinase activities and reduced insulin inhibition of PTEN and glycogen synthase kinase-3 activity. The results demonstrate that cerebellar hypoplasia produced by chronic gestational exposure to ethanol is associated with impaired survival signaling through insulin-regulated pathways, including failure to suppress PTEN function. 相似文献
177.
178.
179.
180.