首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   214篇
  免费   14篇
  2022年   1篇
  2021年   1篇
  2020年   2篇
  2019年   1篇
  2018年   1篇
  2017年   1篇
  2016年   5篇
  2015年   9篇
  2014年   9篇
  2013年   9篇
  2012年   12篇
  2011年   12篇
  2010年   13篇
  2009年   8篇
  2008年   12篇
  2007年   13篇
  2006年   15篇
  2005年   10篇
  2004年   8篇
  2003年   9篇
  2002年   9篇
  2001年   1篇
  2000年   1篇
  1999年   3篇
  1998年   5篇
  1997年   5篇
  1996年   5篇
  1995年   3篇
  1994年   2篇
  1993年   2篇
  1992年   3篇
  1991年   1篇
  1990年   1篇
  1989年   4篇
  1988年   3篇
  1987年   3篇
  1986年   3篇
  1985年   3篇
  1984年   2篇
  1982年   3篇
  1981年   3篇
  1978年   1篇
  1977年   1篇
  1974年   2篇
  1973年   2篇
  1972年   1篇
  1971年   2篇
  1970年   2篇
  1968年   1篇
排序方式: 共有228条查询结果,搜索用时 46 毫秒
141.
Subcommissural organ (SCO)-spondin is a giant glycoprotein of more than 5000 amino acids found in Vertebrata, expressed in the central nervous system and constitutive of Reissner’s fiber. For the first time, in situ hybridization performed on zebrafish (Danio rerio) embryos shows that the gene encoding this protein is expressed transitionally in the floor plate, the ventral midline of the neural tube, and later in the diencephalic third ventricle roof, the SCO. The modular organization of the protein in Echinodermata (Strongylocentrotus purpuratus), Urochordata (Ciona savignyi and C. intestinalis), and Vertebrata (Teleostei, Amphibia, Aves and Mammalia) is also described. As the thrombospondin type 1 repeat motifs represent an increasingly large part of the protein during Deuterostomia evolution, the duplication mechanisms leading to this complex organization are examined. The functional significance of the particularly well-preserved arrangement of the series of SCO-spondin repeat motifs and thombospondin type 1 repeats is discussed. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.  相似文献   
142.
Abstract

In 1609, King Philip III of Spain ordered the expulsion from his kingdom of circa 300,000 Moriscos (Muslims forced to officially convert to Christianity). This expulsion marked the end, and failure, of over a century of concerted efforts by both the Spanish government and Catholic Church to assimilate this minority by destroying its culture. This article explores how the fate of the Moriscos was not inevitable but rather the result of an explosive situation in which (1) faith and culture became conflated and (2) the minority came to be perceived as politically disloyal and a threat to the survival of the state and Church. It draws parallels with the current situation of Muslim communities in contemporary Europe to highlight the similarities between them and to sound a cautionary warning to all Europeans, whatever their creed.  相似文献   
143.

Introduction

Giant cell arteritis (GCA) is characterized by intimal hyperplasia leading to ischaemic manifestations that involve large vessels. Neurotrophins (NTs) and their receptors (NTRs) are protein factors for growth, differentiation and survival of neurons. They are also involved in the migration of vascular smooth muscle cells (VSMCs). Our aim was to investigate whether NTs and NTRs are involved in vascular remodelling of GCA.

Methods

We included consecutive patients who underwent a temporal artery biopsy for suspected GCA. We developed an enzymatic digestion method to obtain VSMCs from smooth muscle cells in GCA patients and controls. Neurotrophin protein and gene expression and functional assays were studied from these VSMCs. Neurotrophin expression was also analysed by immunohistochemistry in GCA patients and controls.

Results

Whereas temporal arteries of both GCA patients (n = 22) and controls (n = 21) expressed nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and sortilin, immunostaining was more intense in GCA patients, especially in the media and intima, while neurotrophin-3 (NT-3) and P75 receptor (P75NTR) were only detected in TA from GCA patients. Expression of TrkB, a BDNF receptor, was higher in GCA patients with ischaemic complications. Serum NGF was significantly higher in GCA patients (n = 28) vs. controls (n = 48), whereas no significant difference was found for BDNF and NT-3. NGF and BDNF enhanced GCA-derived temporal artery VSMC proliferation and BDNF facilitated migration of temporal artery VSMCs in patients with GCA compared to controls.

Conclusions

Our results suggest that NTs and NTRs are involved in vascular remodelling of GCA. In GCA-derived temporal artery VSMC, NGF promoted proliferation and BDNF enhanced migration by binding to TrkB and p75NTR receptors. Further experiments are needed on a larger number of VSMC samples to confirm these results.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-014-0487-z) contains supplementary material, which is available to authorized users.  相似文献   
144.
145.
We used calcium counteracting drugs known to reduce the amplitudeof wound-induced electric wave of depolarization and we showedthat in these conditions, accumulation of the calmodulin mRNA(recently found to be correlated to membrane potential) is stronglyreduced. These results bring additional evidence linking membranepotential and calmodulin mRNA accumulation. 5Present address: North Carolina State University, Departmentof Botany, BOX 7612, Raleigh, NC 27695, U.S.A.  相似文献   
146.
Reassessing the role of phosphocaveolin-1 in cell adhesion and migration   总被引:1,自引:0,他引:1  
Although phosphorylation on tyrosine 14 was identified early in the discovery of caveolin-1, the functional significance of this modification still remains elusive. Recent evidence points to a role of caveolin-1 tyrosine 14 phosphorylation in cell adhesion and migration. These results are based on a variety of tools, including a widely used mouse monoclonal anti-phosphocaveolin-1 antibody, which labels, in cultured cells, a protein localized at or near focal adhesions. We here report results from three independent laboratories, showing that this antibody recognizes phosphocaveolin-1 amongst other proteins in immunoblot analyses and that the signal obtained with this antibody in immunostaining experiments is in part due to labeling of paxillin. Published data need to be interpreted keeping in mind that images of phosphocaveolin-1 cellular localization obtained using this antibody are not valid. We re-evaluate the current knowledge about the role of caveolin-1 in cell adhesion and migration in view of this new information.  相似文献   
147.
Saccharomyces cerevisiae was able to produce 20% (v/v) of ethanol in 45 h in a fully aerated fed-batch process recently developed in our laboratory. A notable feature of this process was a production phase uncoupled to growth, the extent of which was critical for high-level ethanol production. As the level of production was found to be highly variable, we investigated on this high variability by means of a detailed physiological analysis of yeast cells in two fed-batch fermentations showing the most extreme behaviour. We found a massive leakage of intracellular metabolites into the growth medium which correlated with the drop of cell viability. The loss of viability was also found to be proportional to the reduction of plasma membrane phospholipids. Finally, the fed-batch processes with the longest uncoupling phase were characterized by induction of storage carbohydrates at the onset of this phase, whereas this metabolic event was not seen in processes with a short uncoupling phase. Taken together, our results suggested that reproducible high-level bioethanol production in aerated fed-batch processes may be linked to the ability of yeast cells to impede ethanol toxicity by triggering a metabolic remodelling reminiscent to that of cells entering a quiescent GO/G1 state.  相似文献   
148.
149.

Background

Diffuse large B-cell lymphoma (DLBCL) is a common and often fatal malignancy. Immunochemotherapy, a combination of rituximab to standard chemotherapy, has resulted in improved survival. However a substantial proportion of patients still fail to reach sustained remission. We have previously demonstrated that autocrine brain-derived neurotrophic factor (BDNF) production plays a function in human B cell survival, at least partly via sortilin expression. As neurotrophin receptor (Trks) signaling involved activation of survival pathways that are inhibited by rituximab, we speculated that neurotrophins may provide additional support for tumour cell survival and therapeutic resistance in DLBCL.

Methodology/Principal Findings

In the present study, we used two DLBCL cell lines, SUDHL4 and SUDHL6, known to be respectively less and more sensitive to rituximab. We found by RT-PCR, western blotting, cytometry and confocal microscopy that both cell lines expressed, in normal culture conditions, BDNF and to a lesser extent NGF, as well as truncated TrkB and p75NTR/sortilin death neurotrophin receptors. Furthermore, BDNF secretion was detected in cell supernatants. NGF and BDNF production and Trk receptor expression, including TrkA, are regulated by apoptotic conditions (serum deprivation or rituximab exposure). Indeed, we show for the first time that rituximab exposure of DLBCL cell lines induces NGF secretion and that differences in rituximab sensitivity are associated with differential expression patterns of neurotrophins and their receptors (TrkA). Finally, these cells are sensitive to the Trk-inhibitor, K252a, as shown by the induction of apoptosis. Furthermore, K252a exhibits additive cytotoxic effects with rituximab.

Conclusions/Significance

Collectively, these data strongly suggest that a neurotrophin axis, such NGF/TrkA pathway, may contribute to malignant cell survival and rituximab resistance in DLBCL.  相似文献   
150.
Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic example for fine-tuning of the transition between planktonic and community lifestyles through two-component systems (TCS). Here we decipher the regulon of the P. aeruginosa response regulator PprB of the TCS PprAB. We identified genes under the control of this TCS and once this pathway is activated, analyzed and dissected at the molecular level the PprB-dependent phenotypes in various models. The TCS PprAB triggers a hyper-biofilm phenotype with a unique adhesive signature made of BapA adhesin, a Type 1 secretion system (T1SS) substrate, CupE CU fimbriae, Flp Type IVb pili and eDNA without EPS involvement. This unique signature is associated with drug hyper-susceptibility, decreased virulence in acutely infected flies and cytotoxicity toward various cell types linked to decreased Type III secretion (T3SS). Moreover, once the PprB pathway is activated, decreased virulence in orally infected flies associated with enhanced biofilm formation and dissemination defect from the intestinal lumen toward the hemolymph compartment is reported. PprB may thus represent a key bacterial adaptation checkpoint of multicellular and aggregative behavior triggering the production of a unique matrix associated with peculiar antibiotic susceptibility and attenuated virulence, a particular interesting breach for therapeutic intervention to consider in view of possible eradication of P. aeruginosa biofilm-associated infections.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号