全文获取类型
收费全文 | 395篇 |
免费 | 43篇 |
出版年
2021年 | 5篇 |
2019年 | 7篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 15篇 |
2014年 | 14篇 |
2013年 | 18篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 6篇 |
2009年 | 11篇 |
2008年 | 11篇 |
2007年 | 10篇 |
2006年 | 15篇 |
2005年 | 11篇 |
2004年 | 9篇 |
2003年 | 19篇 |
2002年 | 11篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 8篇 |
1998年 | 5篇 |
1997年 | 6篇 |
1995年 | 6篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1976年 | 3篇 |
1975年 | 10篇 |
1974年 | 5篇 |
1970年 | 6篇 |
1969年 | 3篇 |
1968年 | 5篇 |
1966年 | 4篇 |
1965年 | 2篇 |
1963年 | 2篇 |
1961年 | 7篇 |
排序方式: 共有438条查询结果,搜索用时 125 毫秒
1.
In prokaryotes, the RecA protein plays a pivotal role in homologous recombination, catalyzing the transfer of a single DNA
strand into an homologous molecule. Structural homologs of the bacterial RecA protein, called Rad51, have been found in different
eukaryotes (from yeast to man), suggesting a certain level of conservation in recombination pathways among living organisms.
We have cloned the homolog of RAD51 in Caenorhabditis elegans. The CeRAD51 gene is transcribed into two alternative mRNAs and potentially codes for two proteins of 395 and 357 amino acids in length,
respectively. We discuss the evolutionary implications of these findings.
Received: 26 May 1998 / Accepted: 18 August 1998 相似文献
2.
E Imbasciati R Gusmano A Edefonti P Zucchelli C Pozzi C Grassi M Della Volpe F Perfumo P Petrone M Picca et al. 《BMJ (Clinical research ed.)》1985,291(6505):1305-1308
In a multicentre, randomised, prospective trial 89 patients (67 children and 22 adults) with the minimal change nephrotic syndrome were treated with three intravenous pulses of methylprednisolone followed by low dose oral prednisone for six months (group given methylprednisolone) or with high dose oral prednisone for four weeks followed by low dose oral prednisone for five months (control group). Five patients in the group given methylprednisolone and one in the control group did not respond initially. The time to response was shorter in children treated with methylprednisolone. No significant differences between the two groups were observed in the number of patients who relapsed or number of relapses per patient per year. Patients given methylprednisolone tended to relapse earlier than patients in the control group. Side effects related to treatment were significantly fewer in the group given methylprednisolone than in the control group. These data suggest that a short course of methylprednisolone pulses followed by low dose oral prednisone is only marginally less effective than a regimen of high dose oral steroids but can improve the ratio of risk to benefit associated with treatment of the minimal change nephrotic syndrome. 相似文献
3.
4.
Cystine Deprivation Induces Oligodendroglial Death: Rescue by Free Radical Scavengers and by a Diffusible Glial Factor 总被引:4,自引:0,他引:4
Mihoko Yonezawa Stephen A. Back Xiaodong Gan Paul A. Rosenberg Joseph J. Volpe 《Journal of neurochemistry》1996,67(2):566-573
Abstract: In this study we examined the effect on oligodendroglial survival of exogenous cystine deprivation. Oligodendroglia isolated from mixed glial primary cultures derived from brains of 1-day-old rats, and then grown for 3 days, were markedly dependent on extracellular cystine for survival. The EC50 values for cystine for a 24-h exposure ranged from 2 to 65 µ M . After 6 h of cystine deprivation, the cellular glutathione level decreased to 21 ± 13% of the control. Free radical scavengers (α-tocopherol, ascorbate, idebenone, and N-tert -butyl-α-phenylnitrone) were protective against cystine deprivation but had no effect on the glutathione level. An iron chelator, desferrioxamine mesylate, also was protective. These findings suggest that intracellular hydroxyl radicals are important for this toxicity. In contrast to the observations in 3-day-old cultures, the dependence on exogenous cystine for cell viability was not observed consistently in oligodendroglia cultured for 6 days before the onset of cystine deprivation. Several observations suggested that this loss of cystine dependence was due to a diffusible factor. Sensitivity to the toxicity of cystine deprivation in day 6 cultures increased as the volume of medium was increased from 0.3 to 2 ml. Furthermore, preincubation of cystine-depleted medium with astrocyte cultures eliminated the toxicity of the cystine deprivation. HPLC assay of the conditioned cystine-depleted medium showed no significant change in cystine or cysteine concentration. We conclude that oligodendroglia are highly susceptible to cystine deprivation in day 3 cultures and that this susceptibility is due to the accumulation of intracellular free radicals in the setting of glutathione depletion. The resistance of day 6 oligodendroglial cultures is caused at least in part by a diffusible factor. 相似文献
5.
6.
Activation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in homogenates of developing rat brain. 总被引:2,自引:1,他引:1 下载免费PDF全文
The specific activity of 3-hydroxy-3-methylglutaryl-CoA reductase increases when homogenates of developing rat brain are incubated at 37 degrees C or kept on ice. This increase is completely blocked by the addition of F- to the homogenization medium and the assay mixture. The capacity for activation of the reductase is greatest during the early postnatal period and declines as brain maturation proceeds. The data suggest that catalytic modification of the reductase may play a role in the regulation of cholesterol synthesis in the developing brain. 相似文献
7.
In 330 cases of male sterility, the authors found in the seminal fluid 270 cases of quantitative alteration, 196 of qualitative alteration, 62 cases with biochemical disturbances and 122 patients with infections. After the specific treatment of these patients, the result was that 50 to 58.2% of them presented response for the quantitative, qualitative and biochemical alterations. In the infections, the index obtained was 85.2%. Among these 330 cases, they were obtained 73 cases of pregnancy (22.1%) with eight cases of abortion(10.9%). 相似文献
8.
Haiyan Chen Giorgia Valle Sandra Furlan Alma Nani Sandor Gyorke Michael Fill Pompeo Volpe 《The Journal of general physiology》2013,142(2):127-136
Release of Ca2+ from the sarcoplasmic reticulum (SR) drives contractile function of cardiac myocytes. Luminal Ca2+ regulation of SR Ca2+ release is fundamental not only in physiology but also in physiopathology because abnormal luminal Ca2+ regulation is known to lead to arrhythmias, catecholaminergic polymorphic ventricular tachycardia (CPVT), and/or sudden cardiac arrest, as inferred from animal model studies. Luminal Ca2+ regulates ryanodine receptor (RyR)2-mediated SR Ca2+ release through mechanisms localized inside the SR; one of these involves luminal Ca2+ interacting with calsequestrin (CASQ), triadin, and/or junctin to regulate RyR2 function.CASQ2-RyR2 regulation was examined at the single RyR2 channel level. Single RyR2s were incorporated into planar lipid bilayers by the fusion of native SR vesicles isolated from either wild-type (WT), CASQ2 knockout (KO), or R33Q-CASQ2 knock-in (KI) mice. KO and KI mice have CPVT-like phenotypes. We show that CASQ2(WT) action on RyR2 function (either activation or inhibition) was strongly influenced by the presence of cytosolic MgATP. Function of the reconstituted CASQ2(WT)–RyR2 complex was unaffected by changes in luminal free [Ca2+] (from 0.1 to 1 mM). The inhibition exerted by CASQ2(WT) association with the RyR2 determined a reduction in cytosolic Ca2+ activation sensitivity. RyR2s from KO mice were significantly more sensitive to cytosolic Ca2+ activation and had significantly longer mean open times than RyR2s from WT mice. Sensitivity of RyR2s from KI mice was in between that of RyR2 channels from KO and WT mice. Enhanced cytosolic RyR2 Ca2+ sensitivity and longer RyR2 open times likely explain the CPVT-like phenotype of both KO and KI mice. 相似文献
9.
10.
Terry G. Coursey Niral B. Gandhi Eugene A. Volpe Stephen C. Pflugfelder Cintia S. de Paiva 《PloS one》2013,8(11)
CD4+ T cells are essential to pathogenesis of ocular surface disease in dry eye. Two subtypes of CD4+ T cells, Th1 and Th17 cells, function concurrently in dry eye to mediate disease. This occurs in spite of the cross-regulation of IFN-γ and IL-17A, the prototypical cytokines Th1 and Th17 cells, respectively. Essential to an effective immune response are chemokines that direct and summon lymphocytes to specific tissues. T cell trafficking has been extensively studied in other models, but this is the first study to examine the role of chemokine receptors in ocular immune responses. Here, we demonstrate that the chemokine receptors, CCR6 and CXCR3, which are expressed on Th17 and Th1 cells, respectively, are required for the pathogenesis of dry eye disease, as CCR6KO and CXCR3KO mice do not develop disease under desiccating stress. CD4+ T cells from CCR6KO and CXCR3KO mice exposed to desiccating stress (DS) do not migrate to the ocular surface, but remain in the superficial cervical lymph nodes. In agreement with this, CD4+ T cells from CCR6 and CXCR3 deficient donors exposed to DS, when adoptively transferred to T cell deficient recipients manifest minimal signs of dry eye disease, including significantly less T cell infiltration, goblet cell loss, and expression of inflammatory cytokine and matrix metalloproteinase expression compared to wild-type donors. These findings highlight the important interaction of chemokine receptors on T cells and chemokine ligand expression on epithelial cells of the cornea and conjunctiva in dry eye pathogenesis and reveal potential new therapeutic targets for dry eye disease. 相似文献