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   461篇
  免费   25篇
  2022年   3篇
  2021年   13篇
  2020年   3篇
  2019年   10篇
  2018年   6篇
  2017年   9篇
  2016年   11篇
  2015年   19篇
  2014年   28篇
  2013年   40篇
  2012年   41篇
  2011年   38篇
  2010年   26篇
  2009年   19篇
  2008年   29篇
  2007年   25篇
  2006年   22篇
  2005年   17篇
  2004年   19篇
  2003年   21篇
  2002年   15篇
  2001年   1篇
  2000年   5篇
  1999年   3篇
  1998年   6篇
  1997年   5篇
  1996年   5篇
  1995年   4篇
  1994年   5篇
  1993年   3篇
  1992年   2篇
  1991年   3篇
  1990年   2篇
  1989年   4篇
  1988年   3篇
  1986年   6篇
  1985年   1篇
  1984年   1篇
  1983年   1篇
  1980年   2篇
  1979年   4篇
  1973年   1篇
  1970年   1篇
  1969年   2篇
  1963年   1篇
  1961年   1篇
排序方式: 共有486条查询结果,搜索用时 484 毫秒
121.
During embryogenesis, the development of tissues, organs and systems, including the immune system, is particularly susceptible to the effects of noxious agents. We examined the effects of prenatal (in utero) exposure to WiFi signals on pregnancy outcome and the immune B-cell compartment, including antibody production. Sixteen mated (plug-positive) female mice were assigned to each of the following groups: cage control, sham-exposed and microwave-exposed (WiFi signals at 2.45 GHz, whole body, SAR 4 W/kg, 2 h/day, 14 consecutive days starting 5 days after mating). No effects due to exposure to WiFi signals during pregnancy on mating success, number of newborns/mother and body weight at birth were found. Newborn mice were left to grow until 5 or 26 weeks of age, when immunological analyses were performed. No differences due to exposure were found in spleen cell number, B-cell frequency or antibody serum levels. When challenged in vitro with LPS, B cells from all groups produced comparable amounts of IgM and IgG, and proliferated at a similar level. All these findings were consistently observed in the female and male offspring at both juvenile (5 weeks) and adult (26 weeks) ages. Stress-associated effects as well as age- and/or sex-related differences were observed for several parameters. In conclusion, our results do not show any effect on pregnancy outcome or any early or late effects on B-cell differentiation and function due to prenatal exposure to WiFi signals.  相似文献   
122.
The aim of this work was to investigate the effects of exposure to extremely low-frequency electromagnetic fields (ELF-EMF) both on biofilm formation and on mature biofilm of Helicobacter pylori. Bacterial cultures and 2-day-old biofilm of H. pylori ATCC 43629 were exposed to ELF-EMF (50 Hz frequency–1 mT intensity) for 2 days to assess their effect on the cell adhesion and on the mature biofilm detachment, respectively. All the exposed cultures and the respective sham exposed controls were studied for: the cell viability status, the cell morphological analysis, the biofilm mass measurement, the genotypic profile, and the luxS and amiA gene expression. The ELF-EMF acted on the bacterial population during the biofilm formation displaying significant differences in cell viability, as well as, in morphotypes measured by the prevalence of spiral forms (58.41%) in respect to the controls (33.14%), whereas, on mature biofilm, no significant differences were found when compared to the controls. The measurement of biofilm cell mass was significantly reduced in exposed cultures in both examined experimental conditions. No changes in DNA patterns were recorded, whereas a modulation in amiA gene expression was detected. An exposure to ELF-EMF of H. pylori biofilm induces phenotypic changes on adhering bacteria and decreases the cell adhesion unbalancing the bacterial population therefore reducing the H. pylori capability to protect itself.  相似文献   
123.
124.
A new series of synthetic flavones, thioflavones, and flavanones has been synthesized and evaluated as potential inhibitors of monoamine oxidase isoforms (MAO-A and -B). The most active series is the flavanone one with higher selective inhibitory activity against MAO-B. Some of these flavanones (mainly the most effective) have been separated and tested as single enantiomers. In order to investigate the MAOs recognition of the most active and selective compounds, a molecular modeling study has been performed using available Protein Data Bank (PDB) structures as receptor models for docking experiments.  相似文献   
125.

Background

Attention is used to enhance neural processing of selected parts of a visual scene. It increases neural responses to stimuli near target locations and is usually coupled to eye movements. Covert attention shifts, however, decouple the attentional focus from gaze, allowing to direct the attention to a peripheral location without moving the eyes. We tested whether covert attention shifts modulate ongoing neuronal activity in cortical area V6A, an area that provides a bridge between visual signals and arm-motor control.

Methodology/Principal Findings

We performed single cell recordings from 3 Macaca Fascicularis trained to fixate straight-head, while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention. The attentional modulation occurs without gaze shifts and cannot be explained by visual stimulations. Visual, motor, and attentional responses can occur in combination in single neurons.

Conclusions/Significance

This modulation in an area primarily involved in visuo-motor transformation for reaching may form a neural basis for coupling attention to the preparation of reaching movements. Our results show that cortical processes of attention are related not only to eye-movements, as many studies have shown, but also to arm movements, a finding that has been suggested by some previous behavioral findings. Therefore, the widely-held view that spatial attention is tightly intertwined with—and perhaps directly derived from—motor preparatory processes should be extended to a broader spectrum of motor processes than just eye movements.  相似文献   
126.
Using redox proteomics techniques to characterize the thiol status of proteins in human T lymphocytes, we identified cyclophilin A (CypA) as a specifically oxidized protein early after mitogen activation. CypA is an abundantly expressed cytosolic protein, target of the immunosuppressive drug cyclosporin A (CsA), for which a variety of functions has been described. In this study, we could identify CypA as a protein undergoing glutathionylation in vivo. Using MALDI-MS we identified Cys52 and Cys62 as targets of glutathionylation in T lymphocytes, and, using bioinformatic tools, we defined the reasons for the susceptibility of these residues to the modification. In addition, we found by circular dichroism spectroscopy that glutathionylation has an important impact on the secondary structure of CypA. Finally, we suggest that glutathionylation of CypA may have biological implications and that CypA may play a key role in redox regulation of immunity.  相似文献   
127.
Cyclosporine A (CsA) is associated with the development of cardiovascular toxicity in transplant patients but can exert myocardial protection against ischemia/reperfusion damages. We examined in a rat model of chronic CsA administration whether subtle variations in the NO pathway could account for these opposite effects. CsA treatment rapidly led to an increase in myocardial Hsp90 expression promoting the recruitment of Akt and calcineurin, thereby promoting eNOS activation through Ser1177 phosphorylation and Thr495 dephosphorylation, respectively. This was associated with an increase in myocardial VEGF expression and led to anti-apoptotic effects in isolated cardiac myocytes. Upon longer CsA exposure, cardiac toxicity developed, as documented by the infiltration of connective tissue and the increase in iNOS expression. These later effects were associated with a dramatic decrease in the abundance and scaffold function of Hsp90, thereby unraveling the key role of Hsp90 in governing CsA effects.  相似文献   
128.
Miele R  Borro M  Mangoni ML  Simmaco M  Barra D 《Peptides》2003,24(11):1713-1721
In amphibian skin secretions, a peptidylprolyl cis/trans isomerase activity was detected. A Xenopus laevis skin cDNA coding for this protein was cloned, sequenced and over-expressed in Escherichia coli. The primary structure of the protein shows extensive similarity with members of the cyclophilin A family. Catalytic parameters of the recombinant protein are similar to those of the human enzyme. The enzymatic activity is inhibited by cyclosporin A. Data suggesting that peptidylprolyl isomerization influences the biological activity of antibacterial peptides of amphibian origin are presented, and its putative role in the defence mechanism discussed.  相似文献   
129.
Interleukin-6 (IL-6) is a pleiotropic cytokine involved in the regulation of proliferation and differentiation of hematopoietic cells and in the pathogenesis of many diseases, including multiple myeloma. This study pursues a way to interfere with IL-6 pathway in an attempt to modulate its biological activity. Here we describe the rational design and biological evaluation of peptides able to antagonize the murine IL-6 activity by interfering with IL-6 Receptor alpha in 7TD1 cells, a IL-6-dependent B-cell line. Of the peptide tested, only Guess 4a is capable of interfering with IL-6 transducing pathway, therefore inducing growth arrest and apoptosis of 7TD1 cells.  相似文献   
130.
HMGB1 is an architectural factor that enhances the DNA binding affinity of several proteins. We have investigated the influence of HMGB1 on DNA binding by members of the Rel family. HMGB1 enhances DNA binding by p65/p50 and p50/p50, but reduces binding by p65/p65, c-Rel/c-Rel, p65/c-Rel, and p50/c-Rel. In pull-down assays, HMGB1 interacts directly with the p50 subunit via its HMG boxes and this interaction is weakened by the presence of the acidic tail. Functionally, HMGB1 is required for the NF-kappaB-dependent expression of the adhesion molecule VCAM-1.  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