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   641篇
  免费   28篇
  2021年   9篇
  2019年   8篇
  2018年   7篇
  2017年   8篇
  2016年   8篇
  2015年   10篇
  2014年   13篇
  2013年   24篇
  2012年   31篇
  2011年   27篇
  2010年   22篇
  2009年   30篇
  2008年   21篇
  2007年   29篇
  2006年   31篇
  2005年   31篇
  2004年   27篇
  2003年   19篇
  2002年   28篇
  2001年   14篇
  2000年   33篇
  1999年   20篇
  1997年   7篇
  1995年   2篇
  1993年   3篇
  1992年   13篇
  1991年   9篇
  1990年   16篇
  1989年   15篇
  1988年   12篇
  1987年   17篇
  1986年   16篇
  1985年   15篇
  1984年   13篇
  1983年   3篇
  1982年   5篇
  1981年   5篇
  1980年   8篇
  1979年   4篇
  1978年   7篇
  1977年   5篇
  1976年   2篇
  1975年   6篇
  1974年   3篇
  1973年   3篇
  1972年   3篇
  1971年   5篇
  1970年   4篇
  1969年   3篇
  1967年   3篇
排序方式: 共有669条查询结果,搜索用时 718 毫秒
91.
After bilateral carotid glomectomy the rat resistance to acute hypoxia reduces and phenomena of anemia arise. There appear correlations between resistance to hypoxia and red cell count, hemoglobin and hematocrit. The diurnal fluctuation of rat resistance to acute hypoxia after the glomectomy does not change while hemodynamics undergo marked changes.  相似文献   
92.
Drugs of addiction lead to a wide range of epigenetic changes at the promoter regions of genes directly implicated in learning and memory processes. We have previously shown that the histone deactylase inhibitor, sodium butyrate (NaB), accelerates the extinction of nicotine‐seeking and provides resistance to relapse. Here, we explore the potential molecular mechanisms underlying this effect. Rats received intravenous nicotine or saline self‐administration, followed by 6 days of extinction training, with each extinction session followed immediately by treatment with NaB or vehicle. On the last day of extinction, rats were killed and the medial ventral prefrontal cortex retained for chromatin immunoprecipitation and quantitative polymerase chain reaction (qPCR). A history of nicotine exposure significantly decreased H3K14 acetylation at the brain‐derived neurotrophic factor (BDNF) exon IV promoter, and this effect was abolished with NaB treatment. In contrast, nicotine self‐administration alone, resulted in a significant decrease in histone methylation at the H3K27me3 and H3K9me2 marks in the promoter regions of BDNF exon IV and cyclin‐dependent kinase 5 (Cdk‐5). Quantitative PCR‐identified changes in several genes associated with NaB treatment that were independent of nicotine exposure; however, an interaction of nicotine history and NaB treatment was detected only in the expression of BDNF IV and BDNF IX. Together these results suggest that nicotine self‐administration leads to a number of epigenetic changes at both the BDNF and Cdk‐5 promoters, and that these changes may contribute to the enhanced extinction of nicotine‐seeking by NaB.  相似文献   
93.
Skeletal muscle myosin phenotype (i.e., the predominance in the muscle of a particular isoform or isoforms of myosin heavy chains (MyHC)) determines the properties of muscle, such as contraction speed and fatigue. The aim of this study was to identify the functional relationship between the decrease of the nitric oxide (NO) content, the GSK-3β phosphorylation (leading to the GSK-3β activation), the NFATc1 amount in the muscle nuclei, and the MyHC I(β) isoform expression in the rat soleus muscle under gravitational unloading. Male Wistar rats were divided into five groups: the vivarium control group; the group of animals with a 7-day hind limb suspension receiving placebo; the group of animals with a hind limb suspension receiving a NO donor (L-arginine); the group of animals with a hind limb suspension receiving a NO donor and a NO-synthase inhibitor (L-NAME); and the group of animals with a hind limb suspension receiving a GSK-3β inhibitor. We have shown that a 7-day unloading leads to a NO content decrease in the soleus muscle, and this effect is prevented by L-arginine administration. In addition, administration of L-arginine blocks the GSK-3β phosphorylation decrease, NFATc1 export from the muscle nuclei, and MyHC I(β) expression decrease caused by unloading. The L-arginine effect in each case can be blocked by the NO-synthase inhibitor. Administration of the GSK-3β inhibitor prevents the unloading-induced NFATc1 export from the muscle nuclei and a decrease of the MyHC I(β) expression. The prevention of the MyHC I(β) expression decrease and the NFATc1 export from the nucleus by the selective GSK-3β inhibition confirms the hypothesis on the NO influence on the MyHC I(β) expression and the NFATc1 export from the nucleus via the GSK-3β phosphorylation decrease. Thus, the NO level decrease in the rat soleus muscle in unloading leads to the GSK-3β activation, which in turn, promotes the NFATc1 export from the nucleus and stabilization of the fast myosin phenotype.  相似文献   
94.
The functional coupling of protein synthesis and chaperone-assisted folding in vivo has remained largely unexplored. Here we have analysed the chaperonin-dependent folding pathway of actin in yeast. Remarkably, overexpression of a heterologous chaperonin which traps non-native polypeptides does not interfere with protein folding in the cytosol, indicating a high-level organization of folding reactions. Newly synthesized actin avoids the chaperonin trap and is effectively channelled from the ribosome to the endogenous chaperonin TRiC. Efficient actin folding on TRiC is critically dependent on the hetero-oligomeric co-chaperone GimC. By interacting with folding intermediates and with TRiC, GimC accelerates actin folding at least 5-fold and prevents the premature release of non-native protein from TRiC. We propose that TRiC and GimC form an integrated 'folding compartment' which functions in cooperation with the translation machinery. This compartment sequesters newly synthesized actin and other aggregation-sensitive polypeptides from the crowded macromolecular environment of the cytosol, thereby allowing their efficient folding.  相似文献   
95.
The experiments were performed in microcosms situated on a control site and on a site regulated by beavers. Two cladoceran species of different sizes were placed in microcosms in different proportions. It was found that the vital activity products of Castor fiber L. promote an increase in the concentration of total phosphorus (P), a decrease in the N/P ratio in water, and an increase in the chlorophyll a concentration and the abundance and biomass of bacterioplankton. In such conditions, the abundance and biomass of the large species Daphnia (Ctenodaphnia) magna Straus was increased to the greatest extent when compared with background values when it was placed in combination with Ceriodaphnia dubia Richard or without it. Moreover, in the case of the combination of two crustacean species in microcosms, the abundance of C. dubia was lower when compared with the control site, while the abundance of D. magna was higher. The results of a bioassay showed that the productivity of C. dubia decreases in waters where D. magna is most abundant. We concluded that the formation of zooplankton in beaver ponds with specific features determined by the presence of large cladoceran species is provided by changes in the quantitative and qualitative parameters of food resources. This contributes to the massive distribution of large D. magna and its competitive relations with small C. dubia. According to the results of a bioassay, the vital activity products of D. magna can inhibit the fecundity of C. dubia.  相似文献   
96.
In experiments with starving rats (Rattus rattus L.) and rats with alloxan-induced diabetes, the activity of enzymes and the contents of metabolites of the main metabolic pathways have been studied. It has been shown that adaptation of carbohydrate metabolism to these stress conditions has common trends: intensification of gluconeogenetic processes and glyoxylate cycle induction are observed against the background of decrease in the activities of glycolytic enzymes and the pentose phosphate pathway. A hypothetical mechanism of adaptation of rat liver cell metabolism to a deficiency of glucose as the main energy substrate is proposed.  相似文献   
97.
Only a small fraction of spectra acquired in LC-MS/MS runs matches peptides from target proteins upon database searches. The remaining, operationally termed background, spectra originate from a variety of poorly controlled sources and affect the throughput and confidence of database searches. Here, we report an algorithm and its software implementation that rapidly removes background spectra, regardless of their precise origin. The method estimates the dissimilarity distance between screened MS/MS spectra and unannotated spectra from a partially redundant background library compiled from several control and blank runs. Filtering MS/MS queries enhanced the protein identification capacity when searches lacked spectrum to sequence matching specificity. In sequence-similarity searches it reduced by, on average, 30-fold the number of orphan hits, which were not explicitly related to background protein contaminants and required manual validation. Removing high quality background MS/MS spectra, while preserving in the data set the genuine spectra from target proteins, decreased the false positive rate of stringent database searches and improved the identification of low-abundance proteins.  相似文献   
98.
A model that describes the interaction of nonlinear Alfvén packets propagating in opposite directions parallel to the ambient magnetic field is constructed. This model incorporates both (i) the parametric interaction of harmonics propagating in the same direction, which can be responsible for the transportation of the wave energy to the short-wavelength region of the spectrum, and (ii) the parametric interaction of Alfvén waves propagating in opposite directions, which can be responsible for the excitation of backward-propagating waves by the parametric decaylike instability of the forward-propagating fluctuations.  相似文献   
99.
Three systems of monoallelic gene expression in mammals are known, namely, X-chromosome inactivation, imprinting, and allelic exclusion. In all three systems, monoallelic expression is regulated epigenetically and is frequently directed by long non-coding RNAs (ncRNAs). This review briefs all three systems of monoallelic gene expression in mammals focusing on chromatin modifications, spatial chromosome organization in the nucleus, and the functioning of ncRNAs.  相似文献   
100.
A synthetic scheme for preparation of (Gly-Pro) n , (Pro-Gly) n (n = 2, 3), and (Pro-Gly-Pro) n (n = 1, 2) peptides was elaborated. The effect of the synthesized peptides and the Gly-Pro and Pro-Gly dipeptides on survival of cultured cells of PC12 rat pheochromocytoma was studied under the conditions of oxidative stress induced by brief incubation of the cells with hydrogen peroxide. Peptides of the general formula (Gly-Pro) n and the Pro-Gly-Pro peptide at a concentration of 0.2–100 μM were shown to decrease the number of damaged cells. The Gly-Pro peptide was the most active and decreased the number of damaged cells by 49% on average at a concentration of 100 μM.  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