全文获取类型
收费全文 | 511篇 |
免费 | 53篇 |
专业分类
564篇 |
出版年
2022年 | 3篇 |
2021年 | 17篇 |
2020年 | 5篇 |
2019年 | 3篇 |
2018年 | 7篇 |
2017年 | 5篇 |
2016年 | 12篇 |
2015年 | 31篇 |
2014年 | 17篇 |
2013年 | 30篇 |
2012年 | 38篇 |
2011年 | 23篇 |
2010年 | 19篇 |
2009年 | 18篇 |
2008年 | 24篇 |
2007年 | 18篇 |
2006年 | 16篇 |
2005年 | 22篇 |
2004年 | 17篇 |
2003年 | 9篇 |
2002年 | 12篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1993年 | 5篇 |
1992年 | 27篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 16篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1976年 | 3篇 |
1975年 | 5篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1966年 | 2篇 |
1952年 | 2篇 |
1951年 | 2篇 |
1937年 | 2篇 |
排序方式: 共有564条查询结果,搜索用时 15 毫秒
81.
82.
83.
Marina Gabriela Monteiro Carvalho Mori da Cunha Silvia Zia Fanny Oliveira Arcolino Marianne Sylvia Carlon Diego Vilibaldo Beckmann Ney Luis Pippi Dominguita Luhers Gra?a Elena Levtchenko Jan Deprest Jaan Toelen 《PloS one》2015,10(8)
Objectives
Mesenchymal stem cells derived from human amniotic fluid (hAFSCs) are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/R) model and prevent late stage fibrosis.Methods
A total of 45 male 12-wk-old Wistar rats were divided into three equal groups;: rats subjected to I/R injury and treated with Chang Medium, rats subjected to I/R injury and treated with hAFSCs and sham-operated animals. In the first part of this study, hAFSCs that highly expressed CD24, CD117, SIX2 and PAX2 were isolated and characterized. In the second part, renal I/R injury was induced in male rats and cellular treatment was performed 6 hours later via arterial injection. Functional and histological analyses were performed 24 hours, 48 hours and 2 months after treatment using serum creatinine, urine protein to creatinine ratio, inflammatory and regeneration markers and histomorphometric analysis of the kidney. Statistical analysis was performed by analysis of variance followed by the Tukey’s test for multiple comparisons or by nonparametric Kruskal-Wallis followed by Dunn. Statistical significance level was defined as p <0.05.Results
hAFSCs treatment resulted in significantly reduced serum creatinine level at 24 hours, less tubular necrosis, less hyaline cast formation, higher proliferation index, less inflammatory cell infiltration and less myofibroblasts at 48h. The treated group had less fibrosis and proteinuria at 2 months after injury.Conclusion
hAFSCs contain a renal progenitor cell subpopulation that has a nephroprotective effect when delivered intra-arterially in rats with renal I/R injury, and reduces interstitial fibrosis on long term follow-up. 相似文献84.
Sébastien Jacquemont Bradley?P. Coe Micha Hersch Michael?H. Duyzend Niklas Krumm Sven Bergmann Jacques?S. Beckmann Jill?A. Rosenfeld Evan?E. Eichler 《American journal of human genetics》2014,94(3):415-425
Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a “female protective model.” We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in females compared to males (odds ratio [OR] = 1.46, p = 8 × 10−10) in a cohort of 15,585 probands ascertained for NDs. In an independent autism spectrum disorder (ASD) cohort of 762 families, we found a 3-fold increase in deleterious autosomal CNVs (p = 7 × 10−4) and an excess of private deleterious single-nucleotide variants (SNVs) in female compared to male probands (OR = 1.34, p = 0.03). We also showed that the deleteriousness of autosomal SNVs was significantly higher in female probands (p = 0.0006). A similar bias was observed in parents of probands ascertained for NDs. Deleterious CNVs (>400 kb) were maternally inherited more often (up to 64%, p = 10−15) than small CNVs < 400 kb (OR = 1.45, p = 0.0003). In the ASD cohort, increased maternal transmission was also observed for deleterious CNVs and SNVs. Although ASD females showed higher mutational burden and lower cognition, the excess mutational burden remained, even after adjustment for those cognitive differences. These results strongly suggest that females have an increased etiological burden unlinked to rare deleterious variants on the X chromosome. Carefully phenotyped and genotyped cohorts will be required for identifying the symptoms, which show gender-specific liability to mutational burden. 相似文献
85.
86.
Roland Beckmann Ashley M. Toye Jonathan S. Smythe David J. Anstee Michael J.A. Tanner 《Molecular membrane biology》2013,30(3):187-200
Two isoforms of the band 3 anion exchanger are expressed in mammalian cells, a 911 residue protein (B3) in red cells, and a truncated protein (KB3) in the f -intercalated cells of the kidney. Mutants of both isoforms are known to be associated with human disease, and mistargeting of the mutated proteins has been suggested as the mechanism of pathogenesis in several cases but has been difficult to prove. The present study demonstrates the feasibility of using confocal microscopy for investigating the targeting of homozygous and heterozygous B3 and KB3 mutants. K562 erythroleukemia cells offer several advantages for the stable expression of B3, but have not previously been used for its visualization. A wide range of cell attachment factors, growth conditions, fixation reagents and primary antibodies were investigated to enable imaging of B3 and endogenous GPA by immunofluorescence confocal microscopy in stable K562/B3 clones. B3 co-localized with GPA at the cell surface and also in an intracellular compartment. Functional cell surface expression of KB3 in stable K562 clones was also obtained. Importantly, both B3 and KB3 could be expressed as stable fusion proteins tagged with green fluorescent protein (GFP) in K562 cells, and it was demonstrated that N-terminal GFP-tagging does not affect the targeting or chloride transport properties of B3 or KB3. The use of GFP as well as double-labelling methods developed for immunostaining will be invaluable for investigating the interactions of band 3 with itself and other proteins during its trafficking in erythroid and kidney cells. This will help elucidate how band 3 mutations can cause human diseases such as hereditary spherocytosis and distal renal tubular acidosis. 相似文献
87.
88.
89.
90.
Domain movements of elongation factor eEF2 and the eukaryotic 80S ribosome facilitate tRNA translocation 总被引:11,自引:0,他引:11 下载免费PDF全文
Spahn CM Gomez-Lorenzo MG Grassucci RA Jørgensen R Andersen GR Beckmann R Penczek PA Ballesta JP Frank J 《The EMBO journal》2004,23(5):1008-1019
An 11.7-A-resolution cryo-EM map of the yeast 80S.eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges. Sordarin positions domain III of eEF2 so that it can interact with the sarcin-ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation explains the inhibitory action of sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state. A ratchet-like subunit rearrangement (RSR) occurs in the 80S.eEF2.sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes. A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction. 相似文献