全文获取类型
收费全文 | 948篇 |
免费 | 67篇 |
出版年
2023年 | 7篇 |
2022年 | 7篇 |
2021年 | 25篇 |
2020年 | 9篇 |
2019年 | 20篇 |
2018年 | 28篇 |
2017年 | 12篇 |
2016年 | 29篇 |
2015年 | 59篇 |
2014年 | 50篇 |
2013年 | 63篇 |
2012年 | 90篇 |
2011年 | 92篇 |
2010年 | 48篇 |
2009年 | 38篇 |
2008年 | 62篇 |
2007年 | 62篇 |
2006年 | 70篇 |
2005年 | 46篇 |
2004年 | 48篇 |
2003年 | 45篇 |
2002年 | 44篇 |
2001年 | 8篇 |
2000年 | 4篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 7篇 |
1996年 | 9篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有1015条查询结果,搜索用时 15 毫秒
101.
102.
103.
Identification of a novel human granzyme B inhibitor secreted by cultured sertoli cells 总被引:3,自引:0,他引:3
Sipione S Simmen KC Lord SJ Motyka B Ewen C Shostak I Rayat GR Dufour JM Korbutt GS Rajotte RV Bleackley RC 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(8):5051-5058
Sertoli cells have long since been recognized for their ability to suppress the immune system and protect themselves as well as other cell types from harmful immune reaction. However, the exact mechanism or product produced by Sertoli cells that affords this immunoprotection has never been fully elucidated. We examined the effect of mouse Sertoli cell-conditioned medium on human granzyme B-mediated killing and found that there was an inhibitory effect. We subsequently found that a factor secreted by Sertoli cells inhibited killing through the inhibition of granzyme B enzymatic activity. SDS-PAGE analysis revealed that this factor formed an SDS-insoluble complex with granzyme B. Immunoprecipitation and mass spectroscopic analysis of the complex identified a proteinase inhibitor, serpina3n, as a novel inhibitor of human granzyme B. We cloned serpina3n cDNA, expressed it in Jurkat cells, and confirmed its inhibitory action on granzyme B activity. Our studies have led to the discovery of a new inhibitor of granzyme B and have uncovered a new mechanism used by Sertoli cells for immunoprotection. 相似文献
104.
Daher W Browaeys E Pierrot C Jouin H Dive D Meurice E Dissous C Capron M Tomavo S Doerig C Cailliau K Khalife J 《Molecular microbiology》2006,60(3):578-590
The protein called 'suppressor of the dis2 mutant (sds22+)' is an essential regulator of cell division in fission and budding yeasts, where its deletion causes mitotic arrest. Its role in cell cycle control appears to be mediated through the activation of protein phosphatase type 1 (PP1) in Schizosaccharomyces pombe. We have identified the Plasmodium falciparum Sds22 orthologue, which we designated PfLRR1 as it belongs to the leucine-rich repeat protein family. We showed by glutathione-S-transferase pull-down assay that the PfLRR1 gene product interacts with PfPP1, that the PfLRR1-PfPP1 complex is present in parasite extracts and that PfLRR1 inhibits PfPP1 activity. Functional studies in Xenopus oocytes revealed that PfLRR1 interacted with endogenous PP1 and overcame the G2/M cell cycle checkpoint by promoting progression to germinal vesicle breakdown (GVBD). Confirmatory results showing the appearance of GVBD were observed when oocytes were treated with anti-PP1 antibodies or okadaic acid. Taken together, these observations suggest that PfLRR1 can regulate the cell cycle by binding to PP1 and regulating its activity. 相似文献
105.
106.
Aminopeptidase N during the ontogeny of the chick 总被引:1,自引:0,他引:1
Sihn G Savary K Michaud A Fournie-Zaluski MC Roques BP Corvol P Gasc JM 《Differentiation; research in biological diversity》2006,74(2-3):119-128
Little is known about the production and function of metallopeptidases in embryonic development. One such enzyme, aminopeptidase N (APN), is present in several epithelia, the brain and angiogenic vessels in adults. APN promotes vascular growth and endothelial cell proliferation in physiological and pathological models of angiogenesis. However, its possible role in embryonic angiogenesis or other developmental processes is unknown. Its expression profile in the early phase of embryonic development has not been reported. We report here the expression of this enzyme during the early development of the chick embryo, using complementary techniques for monitoring APN mRNA, protein, and enzymatic activity. We detected APN in the embryo as early as gastrulation. In addition to the known sites of APN production identified in both adults and rat fetuses toward the end of gestation, APN was found in unexpected sites, such as the primitive streak, the dorsal folds of the neural tube, the somites, and the primordia of several organs. APN was present mostly in the cardiovascular compartment during the first 13 days of incubation, and in the hematopoietic compartment (yolk sac and aorta-gonad-mesonephros region) early in development. This study provides clues as to the possible role of APN in embryonic development. 相似文献
107.
Preparative laser capture microdissection and single-pot cell wall material preparation: a novel method for tissue-specific analysis 总被引:4,自引:0,他引:4
In adaptation to their function the walls of plant cell display tissue-specific variations of composition according to their developmental stage, cell type and stress of various origin. It is therefore important to obtain a precise analytical data describing the cell wall composition with respect to these different factors. In the present work, laser capture microdissection (LCM) was used for isolating different tissues from the stem of Urtica dioica L. at a semi-preparative scale. The technique was associated for the first time to a one-pot sequential cell wall preparation and hydrolysis for the carbohydrate analysis of each cell type. The results demonstrate that the combination of LCM and micro-analytical methods can provide individual cell type composition and should improve our knowledge of the biochemical diversity of cell walls in plants. This approach will be of potential interest for the understanding of the effects of stress or genetic engineering on the composition of the cell walls. 相似文献
108.
Raimondi MT Moretti M Cioffi M Giordano C Boschetti F Laganà K Pietrabissa R 《Biorheology》2006,43(3-4):215-222
Bioreactors allowing direct-perfusion of culture medium through tissue-engineered constructs may overcome diffusion limitations associated with static culturing, and may provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed on cells within scaffolds is directly dependent on scaffold microstructure and on bioreactor configuration. Aim of this study is to investigate optimal shear stress ranges and to quantitatively predict the levels of hydrodynamic shear imposed to cells during the experiments. Bovine articular chondrocytes were seeded on polyestherurethane foams and cultured for 2 weeks in a direct perfusion bioreactor designed to impose 4 different values of shear level at a single flow rate (0.5 ml/min). Computational fluid dynamics (CFD) simulations were carried out on reconstructions of the scaffold obtained from micro-computed tomography images. Biochemistry analyses for DNA and sGAG were performed, along with electron microscopy. The hydrodynamic shear induced on cells within constructs, as estimated by CFD simulations, ranged from 4.6 to 56 mPa. This 12-fold increase in the level of applied shear stress determined a 1.7-fold increase in the mean content in DNA and a 2.9-fold increase in the mean content in sGAG. In contrast, the mean sGAG/DNA ratio showed a tendency to decrease for increasing shear levels. Our results suggest that the optimal condition to favour sGAG synthesis in engineered constructs, at least at the beginning of culture, is direct perfusion at the lowest level of hydrodynamic shear. In conclusion, the presented results represent a first attempt to quantitatively correlate the imposed hydrodynamic shear level and the invoked biosynthetic response in 3D engineered chondrocyte systems. 相似文献
109.
A Virulence and Antimicrobial Resistance DNA Microarray Detects a High Frequency of Virulence Genes in Escherichia coli Isolates from Great Lakes Recreational Waters
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Katia Hamelin Guillaume Bruant Abdel El-Shaarawi Stephen Hill Thomas A. Edge Sadjia Bekal John Morris Fairbrother Jose Harel Christine Maynard Luke Masson Roland Brousseau 《Applied microbiology》2006,72(6):4200-4206
Escherichia coli is generally described as a commensal species with occasional pathogenic strains. Due to technological limitations, there is currently little information concerning the prevalence of pathogenic E. coli strains in the environment. For the first time, using a DNA microarray capable of detecting all currently described virulence genes and commonly found antimicrobial resistance genes, a survey of environmental E. coli isolates from recreational waters was carried out. A high proportion (29%) of 308 isolates from a beach site in the Great Lakes carried a pathotype set of virulence-related genes, and 14% carried antimicrobial resistance genes, findings consistent with a potential risk for public health. The results also showed that another 8% of the isolates had unusual virulence gene combinations that would be missed by conventional screening. This new application of a DNA microarray to environmental waters will likely have an important impact on public health, epidemiology, and microbial ecology in the future. 相似文献
110.