全文获取类型
收费全文 | 328篇 |
免费 | 58篇 |
专业分类
386篇 |
出版年
2023年 | 3篇 |
2022年 | 2篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 9篇 |
2016年 | 9篇 |
2015年 | 9篇 |
2014年 | 12篇 |
2013年 | 12篇 |
2012年 | 25篇 |
2011年 | 24篇 |
2010年 | 17篇 |
2009年 | 14篇 |
2008年 | 17篇 |
2007年 | 20篇 |
2006年 | 20篇 |
2005年 | 14篇 |
2004年 | 17篇 |
2003年 | 14篇 |
2002年 | 20篇 |
2001年 | 13篇 |
2000年 | 17篇 |
1999年 | 16篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1981年 | 3篇 |
排序方式: 共有386条查询结果,搜索用时 15 毫秒
1.
Gaelle Jan Violaine Delorme Nehm Saksouk Marie Abrivard Virginie Gonzalez Xavier Cayla Mohamed-Ali Hakimi Isabelle Tardieux 《Microbes and infection / Institut Pasteur》2009,11(12):935-945
Toxoplasma gondii is a human protozoan parasite that belongs to the phylum of Apicomplexa and causes toxoplasmosis. As the other members of this phylum, T. gondii obligatory multiplies within a host cell by a peculiar type of mitosis that leads to daughter cell assembly within a mother cell. Although parasite growth and virulence have been linked for years, few molecules controlling mitosis have been yet identified and they include a couple of kinases but not the counteracting phosphatases. Here, we report that in contrast to other animal cells, type 2C is by far the major type of serine threonine phosphatase activity both in extracellular and in intracellular dividing parasites. Using wild type and transgenic parasites, we characterized the 37 kDa TgPP2C molecule as an abundant cytoplasmic and nuclear enzyme with activity being under tight regulation. In addition, we showed that the increase in TgPP2C activity significantly affected parasite growth by impairing cytokinesis while nuclear division still occurred. This study supports for the first time that type 2C protein phosphatase is an important regulator of cell growth in T. gondii. 相似文献
2.
3.
4.
Modeling of adaptations to physical training by using a recursive least squares algorithm 总被引:3,自引:0,他引:3
Busso Thierry; Denis Christian; Bonnefoy Regis; Geyssant Andre; Lacour Jean-Rene 《Journal of applied physiology》1997,82(5):1685-1693
Busso, Thierry, Christian Denis, Régis Bonnefoy,André Geyssant, and Jean-René Lacour. Modeling ofadaptations to physical training by using a recursive least squaresalgorithm. J. Appl. Physiol. 82(5):1685-1693, 1997.The present study assesses the usefulnessof a systems model with time-varying parameters for describing theresponses of physical performance to training. Data for two subjectswho undertook a 14-wk training on a cycle ergometer were used to testthe proposed model, and the results were compared with a model withtime-invariant parameters. Two 4-wk periods of intensive training wereseparated by a 2-wk period of reduced training and followed by a 4-wkperiod of reduced training. The systems input ascribed to the trainingdoses was made up of interval exercises and computed in arbitraryunits. The systems output was evaluated one to five times per week byusing the endurance time at a constant workload. The time-invariantparameters were fitted from actual performances by using the leastsquares method. The time-varying parameters were fitted by using arecursive least squares algorithm. The coefficients of determinationr2 were 0.875 and0.879 for the two subjects using the time-varying model, higher thanthe values of 0.682 and 0.666, respectively, obtained with thetime-invariant model. The variations over time in the model parametersresulting from the expected reduction in the residuals appearedgenerally to account for changes in responses to training. Such a modelwould be useful for investigating the underlying mechanisms ofadaptation and fatigue. 相似文献
5.
6.
Lappalainen I Giliani S Franceschini R Bonnefoy JY Duckett C Notarangelo LD Vihinen M 《Biochemical and biophysical research communications》2000,269(1):124-130
X-linked lymphoproliferative disease (XLP) is a rare and severe immune deficiency, characterized by abnormal immune responses to the Epstein-Barr virus. Recently, the gene responsible for XLP, SH2D1A, has been identified and shown to code for a small cytoplasmic protein with an SH2 domain that interacts with SLAM and 2B4, two receptorial molecules involved in signal transduction in T and NK cells, respectively. A variety of SH2D1A gene mutations have been reported thus far in XLP males. Here we describe a single-strand conformation polymorphism assay for mutation analysis in XLP. Four novel patients with SH2D1A mutations are described. These mutants, and the others previously reported in the literature, have been included in a Registry (SH2D1Abase) that is fully accessible on the World Wide Web. A three-dimensional model of the SH2 domain of the SH2D1A protein has been developed, based on homology with other SH2 domains. The structural consequences of disease-causing SH2D1A mutations are discussed. 相似文献
7.
Binding of YY1 to the proximal region of the murine beta interferon promoter is essential to allow CBP recruitment and K8H4/K14H3 acetylation on the promoter region after virus infection 下载免费PDF全文
Mokrani H Sharaf el Dein O Mansuroglu Z Bonnefoy E 《Molecular and cellular biology》2006,26(22):8551-8561
8.
Analysis of the 5q31-q33 locus shows an association between IL13-1055C/T IL-13-591A/G polymorphisms and Schistosoma haematobium infections 总被引:2,自引:0,他引:2
9.
Aszodi J Rowlands DA Mauvais P Collette P Bonnefoy A Lampilas M 《Bioorganic & medicinal chemistry letters》2004,14(10):2489-2492
Anti-Bredt bridged bicyclo[3.2.1] gamma-lactams were designed as inhibitors of penicillin binding proteins (PBPs). The compounds were prepared by a carbenoid insertion into a lactam N-H bond. Their weak antibacterial activity could either be explained by a poor chemical stability or by unfavorable steric interactions of the methylene bridge of the gamma-lactam with the targeted enzymes. 相似文献
10.
Borland G Edkins AL Acharya M Matheson J White LJ Allen JM Bonnefoy JY Ozanne BW Cushley W 《The Journal of biological chemistry》2007,282(37):27315-27326
CD23 is a type II transmembrane glycoprotein synthesized by hematopoietic cells that has biological activity in both membrane-bound and freely soluble forms, acting via a number of receptors, including integrins. We demonstrate here that soluble CD23 (sCD23) sustains growth of human B cell precursors via an RGD-independent interaction with the alphavbeta5 integrin. The integrin recognizes a tripeptide motif in a small disulfide-bonded loop at the N terminus of the lectin head region of CD23, centered around Arg(172), Lys(173), and Cys(174) (RKC). This RKC motif is present in all forms of sCD23 with cytokine-like activity, and cytokine activity is independent of the lectin head, an "inverse RGD" motif, and the CD21 and IgE binding sites. RKC-containing peptides derived from this region of CD23 bind alphavbeta5 and are biologically active. The binding and activity of these peptides is unaffected by inclusion of a short peptide containing the classic RGD sequence recognized by integrins, and, in far-Western analyses, RKC-containing peptides bind to the beta subunit of the alphavbeta5 integrin. The interaction between alphavbeta5 and sCD23 indicates that integrins deliver to cells important signals initiated by soluble ligands without the requirement for interactions with RGD motifs in their common ligands. This mode of integrin signaling may not be restricted to alphavbeta5. 相似文献