全文获取类型
收费全文 | 194篇 |
免费 | 27篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 7篇 |
2015年 | 9篇 |
2014年 | 6篇 |
2013年 | 12篇 |
2012年 | 17篇 |
2011年 | 7篇 |
2010年 | 7篇 |
2009年 | 13篇 |
2008年 | 13篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 12篇 |
2004年 | 7篇 |
2003年 | 13篇 |
2002年 | 9篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 2篇 |
1958年 | 1篇 |
1954年 | 1篇 |
1949年 | 1篇 |
1943年 | 1篇 |
1942年 | 1篇 |
1939年 | 3篇 |
1938年 | 3篇 |
1937年 | 1篇 |
1936年 | 2篇 |
1933年 | 2篇 |
排序方式: 共有221条查询结果,搜索用时 31 毫秒
1.
2.
3.
AIMS: To investigate the main effects and interactions of different factors : divercin V41 (0-4 ng ml(-1)), NaCl content (0.5-5.5% w v(-1)), phenol (liquid smoke) concentration (0-8 ppm), and pH (5.5-7.5) on Listeria monocytogenes ScottA growth. METHODS AND RESULTS: Experiments were carried out in BHI broth using a central composite design. Divercin V41 (div41), NaCl content and pH were found to be the most influential factors whereas phenol concentration in liquid smoke had no effect on L. monocytogenes ScottA growth in our experimental domain. The combined effects of div41, NaCl content and pH decreased L. monocytogenes ScottA maximum specific growth rate (mu(max)) from 0.34 to 0.01 h(-1) and led to a significant increase in lag time (t(lag)) from 5.5 to 25 h. CONCLUSION: In this study, NaCl, pH and phenol conditions were similar to those currently observed in smoked salmon production. This shows that L. monocytogenes ScottA growth could be efficiently delayed by the use of div41 in addition to the usual technological hurdles. SIGNIFICANCE AND IMPACT OF THE STUDY: In conclusion, the technological hurdles of cold smoked salmon production could be further optimized and combined with the use of div41 or the div41 producer strain to improve the food safety of the product. 相似文献
4.
Mulder J Poland M Gebbink MF Calafat J Moolenaar WH Kranenburg O 《The Journal of biological chemistry》2003,278(29):27216-27223
p116Rip is a ubiquitously expressed protein that was originally identified as a putative binding partner of RhoA in a yeast two-hybrid screen. Overexpression of p116Rip in neuroblastoma cells inhibits RhoA-mediated cell contraction induced by lysophosphatidic acid (LPA); so far, however, the function of p116Rip is unknown. Here we report that p116Rip localizes to filamentous actin (F-actin)-rich structures, including stress fibers and cortical microfilaments, in both serum-deprived and LPA-stimulated cells, with the N terminus (residues 1-382) dictating cytoskeletal localization. In addition, p116Rip is found in the nucleus. Direct interaction or colocalization with RhoA was not detected. We find that p116Rip binds tightly to F-actin (Kd approximately 0.5 microm) via its N-terminal region, while immunoprecipitation assays show that p116Rip is complexed to both F-actin and myosin-II. Purified p116Rip and the F-actin-binding region can bundle F-actin in vitro, as shown by electron microscopy. When overexpressed in NIH3T3 cells, p116Rip disrupts stress fibers and promotes formation of dendrite-like extensions through its N-terminal actin-binding domain; furthermore, overexpressed p116Rip inhibits growth factor-induced lamellipodia formation. Our results indicate that p116Rip is an F-actin-binding protein with in vitro bundling activity and in vivo capability of disassembling the actomyosin-based cytoskeleton. 相似文献
5.
Bouma B Kroon-Batenburg LM Wu YP Brünjes B Posthuma G Kranenburg O de Groot PG Voest EE Gebbink MF 《The Journal of biological chemistry》2003,278(43):41810-41819
Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimer's disease, transmissible spongiform encephalopathies, and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-beta structure. Commonly, fibrillar aggregates are modified by advanced glycation end products (AGE). In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and scavenger receptors A and B type I, and the serine protease tissue-type plasminogen activator (tPA). Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy, we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and thioflavin T and to tPA. In contrast to globular albumin, glycated albumin contains amino acid residues in beta-sheet conformation, as measured with circular dichroism spectropolarimetry. Moreover, it displays cross-beta structure, as determined with x-ray fiber diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand "cross-beta structure" receptors and to tPA. 相似文献
6.
7.
Roovers RC van der Linden E de Bruïne AP Arends JW Hoogenboom HR 《Cancer immunology, immunotherapy : CII》2001,50(1):51-59
Antibodies to tumour-associated antigens are increasingly being used as targeting vehicles for the visualisation and for
therapy of human solid tumours. The epithelial cell adhesion molecule (Ep-CAM) is an antigen that is overexpressed on a variety
of human solid tumours and constitutes an attractive target for immunotargeting. We set out to obtain fully human antibodies
to this antigen by selecting from a large antibody repertoire displayed on bacteriophages. Two single-chain variable antibody
fragments (scFv) were identified that specifically bound recombinant antigen in vitro. One of the selected antibodies (VEL-1)
cross-reacted with extracellular matrix components in immunohistochemistry of colon carcinoma, whereas the other scFv (VEL-2)
specifically recognised colon cancer cells. The latter antibody was further characterised with respect to epitope specificity
and kinetics of antigen-binding. It showed no competition with the well-characterised anti Ep-CAM MOC-31 monoclonal antibody
and had an off-rate of 5 × 10−2 s−1. To obtain an antibody format more suitable for in vivo tumour targeting and to increase the apparent affinity through avidity,
the genes of scFv VEL-2 were re-formatted by fusion to a human (γ1) hinge region and CH3 domain. This “minibody” was expressed
in Escherichia coli, specifically bound the Ep-CAM antigen and showed a 20-fold reduced off-rate in surface plasmon resonance analysis. These
results show that phage antibody selection, combined with antibody engineering, may result in fully human antibody molecules
with promising characteristics for in vivo use in tumour targeting.
Received: 13 July 2000 / Accepted: 12 October 2000 相似文献
8.
Molecular Dissection of the Rho-associated Protein Kinase (p160ROCK)-regulated Neurite Remodeling in Neuroblastoma N1E-115 Cells 总被引:19,自引:0,他引:19 下载免费PDF全文
Masaya Hirose Toshimasa Ishizaki Naoki Watanabe Masayoshi Uehata Onno Kranenburg Wouter H. Moolenaar Fumio Matsumura Midori Maekawa Haruhiko Bito Shuh Narumiya 《The Journal of cell biology》1998,141(7):1625-1636
A critical role for the small GTPase Rho and one of its targets, p160ROCK (a Rho-associated coiled coil-forming protein kinase), in neurite remodeling was examined in neuroblastoma N1E-115 cells. Using wild-type and a dominant-negative form of p160ROCK and a p160ROCK-specific inhibitor, Y-27632, we show here that p160ROCK activation is necessary and sufficient for the agonist-induced neurite retraction and cell rounding. The neurite retraction was accompanied by elevated phosphorylation of myosin light chain and the disassembly of the intermediate filaments and microtubules. Y-27632 blocked both neurite retraction and the elevation of myosin light chain phosphorylation in a similar concentration-dependent manner. On the other hand, suppression of p160ROCK activity by expression of a dominant-negative form of p160ROCK induced neurites in the presence of serum by inducing the reassembly of the intermediate filaments and microtubules. The neurite outgrowth by the p160ROCK inhibition was blocked by coexpression of dominant-negative forms of Cdc42 and Rac, indicating that p160ROCK constitutively and negatively regulates neurite formation at least in part by inhibiting activation of Cdc42 and Rac. The assembly of microtubules and intermediate filaments to form extended processes by inhibitors of the Rho–ROCK pathway was also observed in Swiss 3T3 cells. These results indicate that Rho/ROCK-dependent tonic inhibition of cell process extension is exerted via activation of the actomysin-based contractility, in conjunction with a suppression of assembly of intermediate filaments and microtubules in many cell types including, but not exclusive to, neuronal cells. 相似文献
9.
C. S. Horjus Talabur Horje R. Bruijnen L. Roovers M. J. M. Groenen F. B. M. Joosten P. J. Wahab 《PloS one》2015,10(8)