全文获取类型
收费全文 | 275篇 |
免费 | 8篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 6篇 |
2019年 | 6篇 |
2018年 | 7篇 |
2017年 | 2篇 |
2016年 | 13篇 |
2015年 | 14篇 |
2014年 | 16篇 |
2013年 | 14篇 |
2012年 | 27篇 |
2011年 | 19篇 |
2010年 | 14篇 |
2009年 | 16篇 |
2008年 | 15篇 |
2007年 | 8篇 |
2006年 | 9篇 |
2005年 | 13篇 |
2004年 | 6篇 |
2003年 | 3篇 |
2002年 | 13篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 1篇 |
1992年 | 6篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有283条查询结果,搜索用时 15 毫秒
121.
Vineet Kumar Amira Sharief Ritam Dutta Tanoy Mukherjee Bheem Dutt Joshi Mukesh Thakur Kailash Chandra Bhupendra Singh Adhikari Lalit Kumar Sharma 《Ecology and evolution》2022,12(7)
Brown bear‐mediated conflicts have caused immense economic loss to the local people living across the distribution range. In India, limited knowledge is available on the Himalayan brown bear (HBB), making human–brown bear conflict (HBC) mitigation more challenging. In this study, we studied HBC in the Lahaul valley using a semi‐structured questionnaire survey by interviewing 398 respondents from 37 villages. About 64.8% of respondents reported conflict in two major groups—crop damage (30.6%) and livestock depredations (6.2%), while 28% reported both. Conflict incidences were relatively high in summer and frequently occurred in areas closer to the forest (<500 m) and between the elevations range of 2700 m to 3000 m above sea level (asl). The dependency of locals on forest resources (70%) for their livelihood makes them vulnerable to HBC. The “upper lower” class respondents were most impacted among the various socioeconomic classes. Two of the four clusters were identified as HBC hot spots in Lahaul valley using SaTscan analysis. We also obtained high HBC in cluster II with a 14.35 km radius. We found that anthropogenic food provisioning for HBB, livestock grazing in bear habitats, and poor knowledge of animal behavior among the communities were the major causes of HBC. We suggest horticulture crop waste management, controlled and supervised grazing, ecotourism, the constitution of community watch groups, and others to mitigate HBC. We also recommend notifying a few HBB abundant sites in the valley as protected areas for the long‐term viability of the HBB in the landscape. 相似文献
122.
123.
Aman Gupta Vanashika Sharma Ashish Kumar Tewari Vipul SurenderKumar Gulshan Wadhwa Ashwani Mathur Sanjeev Kumar Sharma Chakresh Kumar Jain 《Bioinformation》2013,9(3):116-120
Pseudomonas aeruginosa is an opportunistic bacterium known for causing chronic infections in cystic fibrosis and chronic obstructive
pulmonary disease (COPD) patients. Recently, several drug targets in Pseudomonas aeruginosa PAO1 have been reported using
network biology approaches on the basis of essentiality and topology and further ranked on network measures viz. degree and
centrality. Till date no drug/ligand molecule has been reported against this targets.In our work we have identified the ligand
/drug molecules, through Orthologous gene mapping against Bacillus subtilis subsp. subtilis str. 168 and performed modelling and
docking analysis. From the predicted drug targets in PA PAO1, we selected those drug targets which show statistically significant
orthology with a model organism and whose orthologs are present in all the selected drug targets of PA PAO1.Modeling of their
structure has been done using I-Tasser web server. Orthologous gene mapping has been performed using Cluster of Orthologs
(COGs) and based on orthology; drugs available for Bacillus sp. have been docked with PA PAO1 protein drug targets using
MoleGro virtual docker version 4.0.2.Orthologous gene for PA3168 gyrA is BS gyrAfound in Bacillus subtilis subsp. subtilis str. 168.
The drugs cited for Bacillus sp. have been docked with PA genes and energy analyses have been made. Based on Orthologous gene
mapping andin-silico studies, Nalidixic acid is reported as an effective drug against PA3168 gyrA for the treatment of CF and
COPD. 相似文献
124.
We investigated the effects of H2O2 generated by glucose (G) and glucose oxidase (GO) on the isolated rabbit aorta suspended in Krebs-Ringer solution. H2O2 produced contraction in small concentration and relaxation followed by contraction in large concentration. Contraction produced by large concentration was smaller than that produced by small concentration of H2O2. Relaxation was prevented by deendothelialization or NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis. These results suggest that H2O2 in large concentrations produces relaxation followed by contraction, and that the relaxation is endothelium-dependent and is mediated by nitric oxide, an endothelium-derived relaxing factor. 相似文献
125.
Sona Pandey Shiv B Tiwari Wricha Tyagi Mali K Reddy Kailash C Upadhyaya Sudhir K Sopory 《European journal of biochemistry》2002,269(13):3193-3204
An immuno-homologue of maize Ca2+/calmodulin (CaM)-dependent protein kinase with a molecular mass of 72 kDa was identified in pea. The pea kinase (PsCCaMK) was upregulated in roots in response to low temperature and increased salinity. Exogenous Ca2+ application increased the kinase level and the response was faster than that obtained following stress application. Low temperature-mediated, but not salinity-mediated stress kinase increase was inhibited by the application of EGTA and W7, a CaM inhibitor. The purification of PsCCaMK using immuno-affinity chromatography resulted in coelution of the kinase with another polypeptide of molecular mass 40 kDa (p40). Western blot revealed the presence of PsCCaMK in nuclear protein extracts and was found to phosphorylate p40 in vitro. Gel mobility shift and South-Western analysis showed that p40 is a DNA-binding protein and it interacted specifically with one of the cis acting elements of the Arabidopsis CaM5 gene (AtCaM5) promoter. The binding of p40 to the specific elements in the AtCaM5 promoter was dependent of its dephosphorylated state. Our results suggest that p40 could be an upstream signal component of the stress responses. 相似文献
126.
Gulshan?Sunavala-Dossabhoy Sri?Kripa?Balakrishnan Siddhartha?Sen Sam?Nuthalapaty Arrigo?De BenedettiEmail author 《BMC molecular biology》2005,6(1):19
Background
The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila or expression of a dominant negative mutant in mouse cells causes loss of nuclear divisions and missegregation of chromosomes probably, due to alterations in chromatin remodeling capacity. Overexpression of TLK1B, a spliced variant of the TLK1 mRNA, in a model mouse cell line increases it's resistance to ionizing radiation (IR) or the radiomimetic drug doxorubicin, also likely due to changes in chromatin remodeling. TLK1B is translationally regulated by the availability of the translation factor eIF4E, and its synthesis is activated by IR. The reason for this mechanism of regulation is likely to provide a rapid means of promoting repair of DSBs. TLK1B specifically phosphorylates histone H3 and Asf1, likely resulting in changes in chromatin structure, particularly at double strand breaks (DSB) sites. 相似文献127.
Vellaichamy E Sommana NK Pandey KN 《Biochemical and biophysical research communications》2005,327(1):106-111
Mice lacking natriuretic peptide receptor-A (NPRA) develop progressive cardiac hypertrophy and congestive heart failure. However, the mechanisms responsible for cardiac hypertrophic growth in the absence of NPRA signaling are not yet known. We sought to determine the activation of nuclear factor-kappaB (NF-kappaB) in Npr1 (coding for NPRA) gene-knockout (Npr1-/-) mice exhibiting cardiac hypertrophy and fibrosis. NF-kappaB binding activity was 4-fold greater in the nuclear extract of Npr1-/- mutant mice hearts as compared with wild-type (Npr1+/+) mice hearts. In parallel, inhibitory kappaB kinase-beta activity and IkappaB-alpha protein phosphorylation were also increased 3- and 4-fold, respectively, in hypertrophied hearts of mutant mice. cGMP levels were significantly reduced 5-fold in plasma and 10-fold in ventricular tissues of mutant mice hearts relative to wild-type controls. The present findings provide direct evidence that ablation of NPRA/cGMP signaling activates NF-kappaB binding activity associated with hypertrophic growth of mutant mice hearts. 相似文献
128.
Background
The protein kinase Target Of Rapamycin (TOR) is a nexus for the regulation of eukaryotic cell growth. TOR assembles into one of two distinct signalling complexes, TOR complex 1 (TORC1) and TORC2 (mTORC1/2 in mammals), with a set of largely non-overlapping protein partners. (m)TORC1 activation occurs in response to a series of stimuli relevant to cell growth, including nutrient availability, growth factor signals and stress, and regulates much of the cell’s biosynthetic activity, from proteins to lipids, and recycling through autophagy. mTORC1 regulation is of great therapeutic significance, since in humans many of these signalling complexes, alongside subunits of mTORC1 itself, are implicated in a wide variety of pathophysiologies, including multiple types of cancer, neurological disorders, neurodegenerative diseases and metabolic disorders including diabetes.Methodology
Recent years have seen numerous structures determined of (m)TOR, which have provided mechanistic insight into (m)TORC1 activation in particular, however the integration of cellular signals occurs upstream of the kinase and remains incompletely understood. Here we have collected and analysed in detail as many as possible of the molecular and structural studies which have shed light on (m)TORC1 repression, activation and signal integration.Conclusions
A molecular understanding of this signal integration pathway is required to understand how (m)TORC1 activation is reconciled with the many diverse and contradictory stimuli affecting cell growth. We discuss the current level of molecular understanding of the upstream components of the (m)TORC1 signalling pathway, recent progress on this key biochemical frontier, and the future studies necessary to establish a mechanistic understanding of this master-switch for eukaryotic cell growth.129.
The ability of ANP to inhibit the hydrolysis of phosphoinositides was examined in [3H] myoinositol-labeled intact murine Leydig tumor (MA-10) cells. Arginine vasopressin (AVP) stimulated the formation of inositol monophosphate (IP1), inositol bisphosphate (IP2), and inositol trisphosphate (IP3) both in a time- and dose- dependent manner in MA-10 cells. ANP inhibited the AVP-induced formation of IP1, IP2, and IP3 in these cells. The inhibitory effect of ANP on the AVP-stimulated formation of IP1, IP2, and IP3 accounted for 30%, 38% and 42%, respectively, which was observed at the varying concentrations of AVP. ANP caused a dose-dependent attenuation in AVP-stimulated production of IP1, IP2 and IP3 with maximum inhibition at 100 nM concentration of ANP. The production of inositol phosphates was inhibited in the presence of 8- bromo cGMP in a dose-dependent manner, whereas dibutyryl-cAMP had no effect on the generation of these metabolites. The LY 83583, an inhibitor of guanylyl cyclase and cGMP production, abolished the inhibitory effect of ANP on the AVP-stimulated production of inositol phosphates. Furthermore, 10 M LY 83583 also inhibited the ANP-stimulated guanylyl cyclase activity and the intracellular accumulation of cGMP by more than 65–70%. The inhibition of eGMP-dependent protein kinase by H-8, significantly restored the levels of AVP-stimulated inositol phosphates in the presence of either ANP or exogenous 8-bromo cGMP. The results of this study suggest that ANP exerts an inhibitory effect on the production of inositol phosphates in murine Leydig tumor (MA-10) cells by mechanisms involving cGMP and cGMP-dependent protein kinase.Established Investigator of the American Heart Association 相似文献
130.
Purpurogallin (PPG) is a phenolic compound extracted from nutgalls formed on oak trees. It has been used as an additive to edible or nonedible oils or fats, and to hydrocarbon fuels or lubricants to retard their oxidation. We investigated by luminoldependent chemiluminescence (PMNL-CL), the ability of PPG to scavenge oxygen free radicals (OFRs) generated by zymosanactivated polympophonuclear leukocytes (PMNLs). Its OFR-scavenging ability was also investigated by the use of nitro blue tetrazolium (NBT). We also investigated by the dye-exclusion method, if PPG affects the viability of PMNLs. PPG in the concentrations of 0.005–0.4 mM was used in this study. PPG scavenged OFRs produced by zymosan-activated PMNLs in a concentration-dependent manner. Almost complete scavenging was observed at a concentration of 0.2 mM. The NBT test indicated that PPG (0.2 mM) did not completely prevent the activation of PMNLs by zymosan. Viability of PMNLs in the absence or presence of PPG (0.4 mM) were 95.77±0.56% and 96.78±0.60% respectively. The results suggest that PPG scavenges OFRs produced from activated PMNLs in a concentration-dependent manner and that the cell viability is not affected by PPG. PPG is a potent scavenger of OFRs and should be of value in the prevention and treatment of diseases in the pathophysiology of which OFRs are involved. ( 相似文献