全文获取类型
收费全文 | 1318篇 |
免费 | 108篇 |
国内免费 | 2篇 |
出版年
2023年 | 6篇 |
2022年 | 9篇 |
2021年 | 46篇 |
2020年 | 20篇 |
2019年 | 31篇 |
2018年 | 29篇 |
2017年 | 39篇 |
2016年 | 56篇 |
2015年 | 89篇 |
2014年 | 75篇 |
2013年 | 108篇 |
2012年 | 102篇 |
2011年 | 112篇 |
2010年 | 75篇 |
2009年 | 50篇 |
2008年 | 70篇 |
2007年 | 63篇 |
2006年 | 55篇 |
2005年 | 54篇 |
2004年 | 66篇 |
2003年 | 57篇 |
2002年 | 47篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1992年 | 4篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 5篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1979年 | 4篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1973年 | 2篇 |
1969年 | 4篇 |
1967年 | 2篇 |
1963年 | 2篇 |
1961年 | 2篇 |
1960年 | 2篇 |
1958年 | 3篇 |
排序方式: 共有1428条查询结果,搜索用时 187 毫秒
61.
Bianca M Bianca S Vecchio I Raffaele R Ingegnosi C Nicoletti F 《Annales de génétique》2003,46(4):467-469
Gerstmann-Str?ussler-Scheinker disease (GSS) is an adult onset, rare, genetically determined autosomal dominant prion disease. Clinically, it is characterized predominantly by slowly progressive spino-cerebellar dysfunction with ataxia, absent reflexes in the legs and cognitive impairment. Onset is usually in the fifth decade and in the early phase, ataxia is predominant. Mutations in the prion protein gene (PRNP) had been identified and the most important of these is at codon 129. A genotype-phenotype relationship with genetic polymorphism at residue 129 between methionine and valine has been supposed. We describe a patient with GSS and P102L-V129 mutation in which the onset with prominent psychiatric features characterized by apathy and depression and not with cerebellar sign and the clinical course with seizures, nor observed in P102L-V129 cases, allow us to confirm observations that the GSS caused by the 102 mutation is influenced by the codon 129 polymorphism with a specific genotype-phenotype influence, but probably other additional factors might be considered as background for phenotypic variability. 相似文献
62.
63.
Photosensitization of HEC1-B cells with a low concentration of hypericin and doses of light below 10 J/cm(2) caused cell death (apoptosis occurred mainly at doses between 2 and 5 J/cm(2), whereas necrosis prevailed above 6 J/cm(2)). However, pre-exposure of cells to innocuous irradiation (2 J/cm(2)) and successive challenge with a light dose that normally induced apoptosis (5 J/cm(2)) altered the expression of the proteins involved in the regulation of apoptosis, stress response and cell cycle. This change resulted in a significant increase in cell photo-tolerance. 相似文献
64.
Ciminelli BM Pompei F Relucenti M Lum JK Simporé J Spedini G Martínez-Labarga C Pardo MG 《Human biology; an international record of research》2002,74(2):243-252
Two polymorphic sites, -107 and -100 with respect to the "cap" site of the human beta globin pseudogene, recently discovered in our laboratory, turned out to have an ethnically complementary distribution. The first site is polymorphic in Europeans, North Africans, Indians (Hindu), and Oriental Asians, and monomorphic in sub-Saharan Africans. Conversely, the second site is polymorphic in sub-Saharan African populations and monomorphic in the aforementioned populations. Here we report the gene frequencies of these two polymorphic sites in nine additional populations (Egyptians, Spaniards, Japanese, Chinese, Filipinos, Vietnamese, Africans from Togo and from Benin, and Pygmies), confirming their ethnospecificity and, through the analysis of these two markers in Oromo and Amhara of Ethiopia (two mixed populations), their usefulness in genetic admixture studies. Moreover, we studied another marker polymorphic in sub-Saharan African populations only, a TaqI restriction fragment length polymorphism located in the same region as the present markers, demonstrating the absence of linkage disequilibrium between it and the -100 site, so that we can exclude that the information they provide is redundant. 相似文献
65.
66.
Astrocytic but not neuronal increased expression and redistribution of parkin during unfolded protein stress 总被引:4,自引:0,他引:4
Parkin is a ubiquitin ligase that facilitates proteasomal protein degradation and is involved in a common autosomal recessive form of Parkinson's disease. Its expression is part of the unfolded protein response in cell lines where its overexpression protects against unfolded protein stress. How parkin expression is regulated in brain primary cells under stress situations is however, less well established. Here, the cellular and subcellular localization of parkin under basal conditions and during unfolded protein stress was investigated in primary cultures of rat astrocytes and hippocampal neurons. Immunofluorescense microscopy and biochemical analysis demonstrated that parkin is mainly associated with the endoplasmic reticulum (ER) in hippocampal neurons while it is associated with Golgi membranes, the nuclei and light vesicles in astrocytes. The constitutive parkin expression was high in neurons as compared with astrocytes. However, unfolded protein stress elicited a selective increase in astrocytic parkin expression and a change in distribution, whereas neuronal parkin remained largely unmodified. The cell specific differences argue in favour of different cellular binding sites and substrates for the protein and a pathogenic role for astrocytes in Parkinson's disease caused by parkin dysfunction. 相似文献
67.
Mabit H Nakano MY Prank U Saam B Döhner K Sodeik B Greber UF 《Journal of virology》2002,76(19):9962-9971
Capsids and the enclosed DNA of adenoviruses, including the species C viruses adenovirus type 2 (Ad2) and Ad5, and herpesviruses, such as herpes simplex virus type 1 (HSV-1), are targeted to the nuclei of epithelial, endothelial, fibroblastic, and neuronal cells. Cytoplasmic transport of fluorophore-tagged Ad2 and immunologically detected HSV-1 capsids required intact microtubules and the microtubule-dependent minus-end-directed motor complex dynein-dynactin. A recent study with epithelial cells suggested that Ad5 was transported to the nucleus and expressed its genes independently of a microtubule network. To clarify the mechanisms by which Ad2 and, as an independent control, HSV-1 were targeted to the nucleus, we treated epithelial cells with nocodazole (NOC) to depolymerize microtubules and measured viral gene expression at different times and multiplicities of infections. Our results indicate that in NOC-treated cells, viral transgene expression was significantly reduced at up to 48 h postinfection (p.i.). A quantitative analysis of subcellular capsid localization indicated that NOC blocked the nuclear targeting of Ad2 and also HSV-1 by more than 90% at up to 7 h p.i. About 10% of the incoming Texas Red-coupled Ad2 (Ad2-TR) was enriched at the nucleus in microtubule-depleted cells at 5 h p.i. This result is consistent with earlier observations that Ad2-TR capsids move randomly in NOC-treated cells at less than 0.1 micro m/s and over distances of less than 5 micro m, characteristic of Brownian motion. We conclude that fluorophore-tagged Ad2 and HSV-1 particles are infectious and that microtubules play a prominent role in efficient nuclear targeting during entry and gene expression of species C Ads and HSV-1. 相似文献
68.
Effects of cytotoxic T lymphocytes (CTL) directed against a single simian immunodeficiency virus (SIV) Gag CTL epitope on the course of SIVmac239 infection 下载免费PDF全文
Allen TM Jing P Calore B Horton H O'Connor DH Hanke T Piekarczyk M Ruddersdorf R Mothé BR Emerson C Wilson N Lifson JD Belyakov IM Berzofsky JA Wang C Allison DB Montefiori DC Desrosiers RC Wolinsky S Kunstman KJ Altman JD Sette A McMichael AJ Watkins DI 《Journal of virology》2002,76(20):10507-10511
Vaccine-induced cytotoxic T lymphocytes (CTL) have been implicated in the control of virus replication in simian immunodeficiency virus (SIV)-challenged and simian-human immunodeficiency virus-challenged macaques. Therefore, we wanted to test the impact that vaccine-induced CTL responses against an immunodominant Gag epitope might have in the absence of other immune responses. By themselves, these strong CTL responses failed to control SIVmac239 replication. 相似文献
69.
Tat-vaccinated macaques do not control simian immunodeficiency virus SIVmac239 replication 总被引:2,自引:0,他引:2 下载免费PDF全文
Allen TM Mortara L Mothé BR Liebl M Jing P Calore B Piekarczyk M Ruddersdorf R O'Connor DH Wang X Wang C Allison DB Altman JD Sette A Desrosiers RC Sutter G Watkins DI 《Journal of virology》2002,76(8):4108-4112
The regulatory proteins of human immunodeficiency virus may represent important vaccine targets. Here we assessed the role of Tat-specific cytotoxic T lymphocytes (CTL) in controlling pathogenic simian immunodeficiency virus SIVmac239 replication after using a DNA-prime, vaccinia virus Ankara-boost vaccine regimen. Despite the induction of Tat-specific CTL, there was no significant reduction in either peak or viral set point compared to that of controls. 相似文献
70.
Redegeld FA van der Heijden MW Kool M Heijdra BM Garssen J Kraneveld AD Van Loveren H Roholl P Saito T Verbeek JS Claassens J Koster AS Nijkamp FP 《Nature medicine》2002,8(7):694-701
Immunoglobulin (Ig)-free light chains IgLC are present in serum and their production is augmented under pathological conditions such as multiple sclerosis, rheumatoid arthritis and neurological disorders. Until now, no (patho)physiological function has been ascribed to circulating Ig light chains. Here we show that IgLCs can confer mast cell dependent hypersensitivity in mice. Antigenic stimulation results in plasma extravasation, cutaneous swelling and mast-cell degranulation. We show that IgLCs have a crucial role in development of contact sensitivity, which could be completely prevented by a novel IgLC antagonist. Although IgE and IgG(1) are central to the induction of immediate hypersensitivity reactions, our results show that IgLCs have similar activity. IgLCs may therefore be a novel factor in the humoral immune response to antigen exposure. Our findings open new avenues in investigating the pathogenesis of autoimmune diseases and their treatments. 相似文献