全文获取类型
收费全文 | 1003篇 |
免费 | 85篇 |
国内免费 | 3篇 |
出版年
2023年 | 12篇 |
2022年 | 12篇 |
2021年 | 30篇 |
2020年 | 33篇 |
2019年 | 26篇 |
2018年 | 31篇 |
2017年 | 28篇 |
2016年 | 37篇 |
2015年 | 69篇 |
2014年 | 69篇 |
2013年 | 76篇 |
2012年 | 114篇 |
2011年 | 103篇 |
2010年 | 50篇 |
2009年 | 48篇 |
2008年 | 63篇 |
2007年 | 56篇 |
2006年 | 54篇 |
2005年 | 45篇 |
2004年 | 32篇 |
2003年 | 31篇 |
2002年 | 33篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1984年 | 2篇 |
1982年 | 3篇 |
1970年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有1091条查询结果,搜索用时 15 毫秒
991.
Laury Lescat Amaury Herpin Brigitte Mourot Vincent Véron Yann Guiguen Julien Bobe 《Autophagy》2018,14(7):1267-1270
Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis essential for the control of intermediary metabolism. So far, the absence of any identifiable LAMP2A – a necessary and limiting protein for CMA – outside of the tetrapod clade, led to the paradigm that this cellular function was (presumably) restricted to mammals and birds. However, after we identified expressed sequences displaying high sequence homology with the mammalian LAMP2A in several fish species, our findings challenge that view and suggest that CMA likely appeared much earlier during evolution than initially thought. Hence, our results do not only shed an entirely new light on the evolution of CMA, but also bring new perspectives on the possible use of complementary genetic models, such as zebrafish or medaka for studying CMA function from a comparative angle/view. 相似文献
992.
An aminoacylase activity from Streptomyces ambofaciens catalyzes the acylation of lysine on α‐position and peptides on N‐terminal position 下载免费PDF全文
Léna Dettori Florent Ferrari Xavier Framboisier Cédric Paris Yann Guiavarc'h Laurence Hôtel Arnaud Aymes Pierre Leblond Catherine Humeau Romain Kapel Isabelle Chevalot Stéphane Delaunay 《Engineering in Life Science》2018,18(8):589-599
The presence of aminoacylase activities was investigated in a crude extract of Streptomyces ambofaciens ATCC23877. First activities catalyzing the hydrolysis of N‐α or ε‐acetyl‐L‐lysine were identified. Furthermore, the acylation of lysine and different peptides was studied and compared with results obtained with lipase B of Candida antarctica (CALB). Different regioselectivities were demonstrated for the two classes of enzymes. CALB was able to catalyze acylation only on the ε‐position whereas the crude extract from S. ambofaciens possessed the rare ability to catalyze the N‐acylation on the α‐position of the lysine or of the amino‐acid in N‐terminal position of peptides. Two genes, SAM23877_1485 and SAM23877_1734, were identified in the genome of Streptomyces ambofaciens ATCC23877 whose products show similarities with the previously identified aminoacylases from Streptomyces mobaraensis. The proteins encoded by these two genes were responsible for the major aminoacylase hydrolytic activities. Furthermore, we show that the hydrolysis of N‐α‐acetyl‐L‐lysine could be attributed to the product of SAM23877_1734 gene. 相似文献
993.
David Daniel Scott Emma S. M. Boston Mathieu G. Lundy Daniel J. Buckley Yann Gager Callum J. Chaplain Emma C. Teeling William Ian Montgomery Paulo A. Prodöhl 《Population Ecology》2018,60(4):361-370
Given their cryptic behaviour, it is often difficult to establish kinship within microchiropteran maternity colonies. This limits understanding of group formation within this highly social group. Following a concerted effort to comprehensively sample a Natterer’s bat (Myotis nattereri) maternity colony over two consecutive summers, we employed microsatellite DNA profiling to examine genetic relatedness among individuals. Resulting data were used to ascertain female kinship, parentage, mating strategies, and philopatry. Overall, despite evidence of female philopatry, relatedness was low both for adult females and juveniles of both sexes. The majority of individuals within the colony were found to be unrelated or distantly related. However, parentage analysis indicates the existence of a number of maternal lineages (e.g., grandmother, mother, or daughter). There was no evidence suggesting that males born within the colony are mating with females of the same colony. Thus, in this species, males appear to be the dispersive sex. In the Natterer’s bat, colony formation is likely to be based on the benefits of group living, rather than kin selection. 相似文献
994.
995.
ABA transport and transporters 总被引:1,自引:0,他引:1
996.
Nicolas Denancé Philippe Ranocha Nicolas Oria Xavier Barlet Marie‐Pierre Rivière Koste A. Yadeta Laurent Hoffmann François Perreau Gilles Clément Alessandra Maia‐Grondard Grardy C.M. van den Berg Bruno Savelli Sylvie Fournier Yann Aubert Sandra Pelletier Bart P.H.J. Thomma Antonio Molina Lise Jouanin Yves Marco Deborah Goffner 《The Plant journal : for cell and molecular biology》2013,73(2):225-239
997.
Shahzina Kanwal Yann Fardini Patrick Pagesy Thierry N’Tumba-Byn Cécile Pierre-Eugène Elodie Masson Cornelia Hampe Tarik Issad 《PloS one》2013,8(7)
O-GlcNAcylation (addition of N-acetyl-glucosamine on serine or threonine
residues) is a post-translational modification that regulates stability,
activity or localization of cytosolic and nuclear proteins. O-linked
N-acetylgluocosmaine transferase (OGT) uses UDP-GlcNAc, produced in the
hexosamine biosynthetic pathway to O-GlcNacylate proteins. Removal of O-GlcNAc
from proteins is catalyzed by the β-N-Acetylglucosaminidase (OGA). Recent
evidences suggest that O-GlcNAcylation may affect the growth of cancer cells.
However, the consequences of O-GlcNAcylation on anti-cancer therapy have not
been evaluated. In this work, we studied the effects of O-GlcNAcylation on
tamoxifen-induced cell death in the breast cancer-derived MCF-7 cells.
Treatments that increase O-GlcNAcylation (PUGNAc and/or glucosoamine) protected
MCF-7 cells from death induced by tamoxifen. In contrast, inhibition of OGT
expression by siRNA potentiated the effect of tamoxifen on cell death. Since the
PI-3 kinase/Akt pathway is a major regulator of cell survival, we used BRET to
evaluate the effect of PUGNAc+glucosamine on PIP3 production. We
observed that these treatments stimulated PIP3 production in MCF-7
cells. This effect was associated with an increase in Akt phosphorylation.
However, the PI-3 kinase inhibitor , which abolished the effect of
PUGNAc+glucosamine on Akt phosphorylation, did not impair the protective effects
of PUGNAc+glucosamine against tamoxifen-induced cell death. These results
suggest that the protective effects of O-GlcNAcylation are independent of the
PI-3 kinase/Akt pathway. As tamoxifen sensitivity depends on the estrogen
receptor (ERα) expression level, we evaluated the effect of PUGNAc+glucosamine
on the expression of this receptor. We observed that O-GlcNAcylation-inducing
treatment significantly reduced the expression of ERα mRNA and protein,
suggesting a potential mechanism for the decreased tamoxifen sensitivity induced
by these treatments. Therefore, our results suggest that inhibition of
O-GlcNAcylation may constitute an interesting approach to improve the
sensitivity of breast cancer to anti-estrogen therapy. LY294002相似文献
998.
999.
Unraveling the Role of Surface Mucus-Binding Protein and Pili in Muco-Adhesion of Lactococcus lactis
Doan Thanh Lam Le Thi-Ly Tran Marie-Pierre Duviau Mickael Meyrand Yann Guérardel Micka?l Castelain Pascal Loubière Marie-Pierre Chapot-Chartier Etienne Dague Muriel Mercier-Bonin 《PloS one》2013,8(11)
Adhesion of bacteria to mucus may favor their persistence within the gut and their beneficial effects to the host. Interactions between pig gastric mucin (PGM) and a natural isolate of Lactococcus lactis (TIL448) were measured at the single-cell scale and under static conditions, using atomic force microscopy (AFM). In parallel, these interactions were monitored at the bacterial population level and under shear flow. AFM experiments with a L. lactis cell-probe and a PGM-coated surface revealed a high proportion of specific adhesive events (60%) and a low level of non-adhesive ones (2%). The strain muco-adhesive properties were confirmed by the weak detachment of bacteria from the PGM-coated surface under shear flow. In AFM, rupture events were detected at short (100−200 nm) and long distances (up to 600−800 nm). AFM measurements on pili and mucus-binding protein defective mutants demonstrated the comparable role played by these two surface proteinaceous components in adhesion to PGM under static conditions. Under shear flow, a more important contribution of the mucus-binding protein than the pili one was observed. Both methods differ by the way of probing the adhesion force, i.e. negative force contact vs. sedimentation and normal-to-substratum retraction vs. tangential detachment conditions, using AFM and flow chamber, respectively. AFM blocking assays with free PGM or O-glycan fractions purified from PGM demonstrated that neutral oligosaccharides played a major role in adhesion of L. lactis TIL448 to PGM. This study dissects L. lactis muco-adhesive phenotype, in relation with the nature of the bacterial surface determinants. 相似文献
1000.
Yann Reynaud Steven Pitchford Sophie De Decker Gary H. Wikfors Christopher L. Brown 《PloS one》2013,8(12)
Vibrio vulnificus is a ubiquitous marine bacterium that is responsible for infections and some seafood-related illnesses and deaths in the United States, mainly in individuals with compromised health status in the Gulf of Mexico region. Most phylogenetic studies focus on V. vulnificus strains isolated in the southern United States, but almost no genetic data are available on northeastern bacterial isolates of clinical or environmental origin. Our goal in this study was to examine the genetic diversity of environmental strains isolated from commercially-produced oysters and in clinical strains of known pathogenicity in northeastern United States. We conducted analyses of a total of eighty-three strains of V. vulnificus, including 18 clinical strains known to be pathogenic. A polyphasic, molecular-typing approach was carried out, based upon established biotypes, vcg, CPS, 16S rRNA types and three other genes possibly associated with virulence (arylsulfatase A, mtlABC, and nanA). An established Multi Locus Sequence Typing (MLST) method was also performed. Phylogenetic analyses of these markers and MLST results produced similar patterns of clustering of strains into two main lineages (we categorized as ‘LI’ and ‘LII’), with clinical and environmental strains clustering together in both lineages. Lineage LII was comprised primarily but not entirely of clinical bacterial isolates. Putative virulence markers were present in both clinical and environmental strains. These results suggest that some northeastern environmental strains of V. vulnificus are phylogenetically close to clinical strains and probably are capable of virulence. Further studies are necessary to assess the risk of human illness from consuming raw oysters harvested in the northeastern US. 相似文献