全文获取类型
收费全文 | 267篇 |
免费 | 21篇 |
专业分类
288篇 |
出版年
2023年 | 2篇 |
2022年 | 9篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 11篇 |
2018年 | 16篇 |
2017年 | 10篇 |
2016年 | 15篇 |
2015年 | 6篇 |
2014年 | 22篇 |
2013年 | 20篇 |
2012年 | 14篇 |
2011年 | 21篇 |
2010年 | 10篇 |
2009年 | 15篇 |
2008年 | 11篇 |
2007年 | 4篇 |
2006年 | 4篇 |
2005年 | 3篇 |
2004年 | 4篇 |
2003年 | 2篇 |
2002年 | 4篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 7篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1982年 | 6篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有288条查询结果,搜索用时 0 毫秒
11.
12.
The rad16 gene of Schizosaccharomyces pombe: a homolog of the RAD1 gene of Saccharomyces cerevisiae. 总被引:4,自引:2,他引:4 下载免费PDF全文
A M Carr H Schmidt S Kirchhoff W J Muriel K S Sheldrick D J Griffiths C N Basmacioglu S Subramani M Clegg A Nasim et al. 《Molecular and cellular biology》1994,14(3):2029-2040
The rad10, rad16, rad20, and swi9 mutants of the fission yeast Schizosaccharomyces pombe, isolated by their radiation sensitivity or abnormal mating-type switching, have been shown previously to be allelic. We have cloned DNA correcting the UV sensitivity or mating-type switching phenotype of these mutants and shown that the correcting DNA is encompassed in a single open reading frame. The gene, which we will refer to as rad16, is approximately 3 kb in length, contains seven introns, and encodes a protein of 892 amino acids. It is not essential for viability of S. pombe. The predicted protein is the homolog of the Saccharomyces cerevisiae RAD1 protein, which is involved in an early step in excision-repair of UV damage from DNA. The approximately 30% sequence identity between the predicted proteins from the two yeasts is distributed throughout the protein. Two-hybrid experiments indicate a strong protein-protein interaction between the products of the rad16 and swi10 genes of S. pombe, which mirrors that reported for RAD1 and RAD10 in S. cerevisiae. We have identified the mutations in the four alleles of rad16. They mapped to the N-terminal (rad10), central (rad20), and C-terminal (rad16 and swi9) regions. The rad10 and rad20 mutations are in the splice donor sequences of introns 2 and 4, respectively. The plasmid correcting the UV sensitivity of the rad20 mutation was missing the sequence corresponding to the 335 N-terminal amino acids of the predicted protein. Neither smaller nor larger truncations were, however, able to correct its UV sensitivity. 相似文献
13.
Leah?C.?Solberg Amber?E.?Baum Nasim?Ahmadiyeh Kazuhiro?Shimomura Renhua?Li Fred?W.?Turek Gary?A.?Churchill Joseph?S.?Takahashi Eva?E.?RedeiEmail author 《Mammalian genome》2004,15(8):648-662
The Wistar–Kyoto (WKY) rat exhibits physiological and behavioral similarities to endophenotypes of human depression. In the forced swim test (FST), a well-characterized antidepressant-reversible test for behavioral despair in rodents, WKYs express characteristics of behavioral despair; increased immobility, and decreased climbing. To map genetic loci linked to behavior in the FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2 generation of a WKY × Fisher 344 (F344) reciprocal intercross. Using linear-model-based genome scans to include covariate (sex or lineage)-by-QTL interaction effects, four significant QTL influencing climbing behavior were identified. In addition, we identified three, seven, and two suggestive QTL for climbing, immobility, and swimming, respectively. One of these loci was pleiotropic, affecting both immobility and climbing. As found in human linkage studies, several of these QTL showed sex- and/or lineage-dependent effects. A simultaneous search strategy identified three epistatic locus pairs for climbing. Multiple regression analysis was employed to characterize the joint contributions of these QTL and to clarify the sex- and lineage-dependent effects. As expected for complex traits, FST behavior is influenced by multiple QTL of small effect, each contributing 5%–10%, accounting for a total 10%–30% of the phenotypic variance. A number of loci mapped in this study share overlapping candidate regions with previously identified emotionality QTL in mice as well as with susceptibility loci recognized by linkage or genome scan analyses for major depression or bipolar disorder in humans. The presence of these loci across species suggests that these QTL may represent universal genetic factors contributing to mood disorders. 相似文献
14.
Muhammad Saqib Javaid Akhtar Ghulam Abbas Muhammad Nasim 《Acta Physiologiae Plantarum》2013,35(9):2761-2768
Salinity and drought are important agro-environmental problems occurring separately as well as together with the combined occurrence increasing with time due to climate change. Screening of bread wheat genotypes against salinity or drought alone is common; however, little information is available on the response of wheat genotypes to a combination of these stresses. This study investigates the response of a salt-resistant (SARC-1) and a salt-sensitive (7-Cerros) wheat genotype to drought at different growth stages under non-saline (ECe 2.1 dS m?1) and saline soil (ECe 15 dS m?1) conditions. Drought was applied by withholding water for 21 days at a particular growth stage viz. tillering, booting, and grain filling stages. At booting stage measurements regarding water relations, leaf ionic composition and photosynthetic attributes were made. At maturity grain yield and different yield, components were recorded. Salinity and drought significantly decreased grain yield and different yield components with a higher decrease in the case of combined stress of salinity × drought. The complete drought treatment (drought at tillering + booting + grain filling stages) was most harmful for wheat followed by drought at booting stage and grain filling–tillering stages, respectively. The salt-resistant wheat genotype SARC-1 performed better than the salt-sensitive genotype 7-Cerros in different stress treatments. A decrease in the water and turgor potentials, photosynthetic and transpiration rates, stomatal conductance, leaf K+, and increased leaf Na+ were the apparent causes of growth and yield reduction of bread wheat due to salinity, drought, and salinity × drought. 相似文献
15.
Summary Glucagon increased alanine amino transferase (AAT) activity in perfused rat liver by about 90% over control. Propranolol, the beta receptor antagonist, abolished the effect of glucagon on this enzyme. Well known beta receptor agonists like isoproterenol, norepinephrine and epinephrine also increased the enzyme activity under identical condition and the enhancement was similarly abolished by propranolol. These experiments suggest that the effect of glucagon on AAT was mediated through beta adrenergic receptor. However, the interesting observation was that phenylephrine, alpha receptor agonist and phenoxybenzamine and tolazoline, two alpha receptor antagonists, increased the AAT activity like glucagon in perfusion experiments and the effects of all these three agents were also abolished by propranolol. Glucagon, when perfused with phenoxybenzamine showed some additive effect. From all these results we are proposing that in our system phenoxybenzamine is acting as beta agonist although it is known to be an alpha antagonist. 相似文献
16.
Combinatorial splicing of exon pairs by two-site binding of U1 small nuclear ribonucleoprotein particle. 总被引:8,自引:8,他引:8 下载免费PDF全文
A two-site model for the binding of U1 small nuclear ribonucleoprotein particle (U1 snRNP) was tested in order to understand how exon partners are selected in complex pre-mRNAs containing alternative exons. In this model, it is proposed that two U1 snRNPs define a functional unit of splicing by base pairing to the 3' boundary of the downstream exon as well as the 5' boundary of the intron to be spliced. Three-exon substrates contained the alternatively spliced exon 4 (E4) region of the preprotachykinin gene. Combined 5' splice site mutations at neighboring exons demonstrate that weakened binding of U1 snRNP at the downstream site and improved U1 snRNP binding at the upstream site result in the failure to rescue splicing of the intron between the mutations. These results indicate the stringency of the requirement for binding a second U1 snRNP to the downstream 5' splice site for these substrates as opposed to an alternative model in which a certain threshold level of U1 snRNP can be provided at either site. Further support for the two-site model is provided by single-site mutations in the 5' splice site of the third exon, E5, that weaken base complementarity to U1 RNA. These mutations block E5 branchpoint formation and, surprisingly, generate novel branchpoints that are specified chiefly by their proximity to a cryptic 5' splice site located at the 3' terminus of the pre-mRNA. The experiments shown here demonstrate a true stimulation of 3' splice site activity by the downstream binding of U1 snRNP and suggest a possible mechanism by which combinatorial patterns of exon selection are achieved for alternatively spliced pre-mRNAs. 相似文献
17.
Linlin Zhong Tsung-Yin J. Yeh Jun Hao Nasim Pourtabatabaei Sushil K. Mahata Jianhua Shao Steven D. Chessler Nai-Wen Chi 《PloS one》2015,10(4)
The poly-ADP-ribosylation (PARsylation) activity of tankyrase (TNKS) regulates diverse physiological processes including energy metabolism and wnt/β-catenin signaling. This TNKS activity uses NAD+ as a co-substrate to post-translationally modify various acceptor proteins including TNKS itself. PARsylation by TNKS often tags the acceptors for ubiquitination and proteasomal degradation. Whether this TNKS activity is regulated by physiological changes in NAD+ levels or, more broadly, in cellular energy charge has not been investigated. Because the NAD+ biosynthetic enzyme nicotinamide phosphoribosyltransferase (NAMPT) in vitro is robustly potentiated by ATP, we hypothesized that nutritional energy might stimulate cellular NAMPT to produce NAD+ and thereby augment TNKS catalysis. Using insulin-secreting cells as a model, we showed that glucose indeed stimulates the autoPARsylation of TNKS and consequently its turnover by the ubiquitin-proteasomal system. This glucose effect on TNKS is mediated primarily by NAD+ since it is mirrored by the NAD+ precursor nicotinamide mononucleotide (NMN), and is blunted by the NAMPT inhibitor FK866. The TNKS-destabilizing effect of glucose is shared by other metabolic fuels including pyruvate and amino acids. NAD+ flux analysis showed that glucose and nutrients, by increasing ATP, stimulate NAMPT-mediated NAD+ production to expand NAD+ stores. Collectively our data uncover a metabolic pathway whereby nutritional energy augments NAD+ production to drive the PARsylating activity of TNKS, leading to autoPARsylation-dependent degradation of the TNKS protein. The modulation of TNKS catalytic activity and protein abundance by cellular energy charge could potentially impose a nutritional control on the many processes that TNKS regulates through PARsylation. More broadly, the stimulation of NAD+ production by ATP suggests that nutritional energy may enhance the functions of other NAD+-driven enzymes including sirtuins. 相似文献
18.
Shahid Ali Naeem Khan Faisal Nouroz Shazia Erum Wajid Nasim Muhammd Adnan Shahid 《In vitro cellular & developmental biology. Plant》2018,54(1):104-111
Improvement of potato has been accomplished using conventional and non-conventional approaches coupled with numerous tissue culture procedures. The aim of the present study was to assess the efficacy of gibberellic acid (GA3) on the morphogenesis of International Potato Center (CIP) potato explants and acclimatization of plantlets in the field. Nodal segments as an explant source (1–1.5 cm) were isolated from 31 CIP potato plantlets and were inoculated into Murashige and Skoog (MS) medium supplemented with 0.0 (control), 0.1, 0.5, or 1.0 mg L?1of GA3. The variation in growth parameters of the cultivars was then observed. The highest shoot induction occurred in MS medium containing 1.0 mg L?1 GA3 with an increase in the inter-nodal distance between nodes as compared to other treatments. Higher concentration (1.0 mg L?1) of GA3 significantly increased plant height and root length in the treated germplasm however; this concentration was inhibitory to the number of nodes and roots per plant. The number of leaves was significantly increased in plants receiving GA3 treatment at lower concentration (0.1 mg L?1). The 31 CIP genotypes were transplanted to the field and checked for yield quality traits. It was concluded from the results that GA3 had significant effects on morphogenesis and was effective in the acclimatization of CIP potato plantlets in field. 相似文献
19.
Time‐lapse microscopy of oxidative stress demonstrates metabolic sensitivity of retinal pericytes under high glucose condition 下载免费PDF全文
Hyperglycemia affects retinal vascular cell function, promotes the development and progression of diabetic retinopathy and ultimately causes vision loss. Oxidative stress, reactive oxygen species (ROS) in excess, is a key biomarker for diabetic retinopathy. Using time‐lapse fluorescence microscopy, ROS dynamics was monitored and the metabolic resistivity of retinal endothelial cells (REC) and pericytes (RPC) was compared under metabolic stress conditions including high glucose (HG). In the presence of a mitochondrial stressor, REC exhibited a significant increase in the rate of ROS production compared with RPC. Thus, under normal glucose (NG), REC may utilize oxidative metabolism as the bioenergetic source, while RPC metabolic activity is independent of mitochondrial respiration. In HG condition, the rate of ROS production in RPC was significantly higher, whereas this rate remained unchanged in REC. Thus, under HG condition RPC may preferentially utilize oxidative metabolism, which results in increased rate of ROS production. In contrast, REC use glycolysis as their major bioenergetic source for ATP production, and consequently HG minimally affects their ROS levels. These observations are consistent with our previous studies where we showed HG condition has minimal effect on apoptosis of REC, but results in increased rate of apoptosis in RPC. Collectively, our results suggest that REC and RPC exhibit different metabolic activity preferences under different glucose conditions. Thus, protection of RPC from oxidative stress may provide an early point of intervention in development and progression of diabetic retinopathy. 相似文献
20.
Felipe Gazos-Lopes Mauricio M. Oliveira Lucas V. B. Hoelz Danielle P. Vieira Alexandre F. Marques Ernesto S. Nakayasu Marta T. Gomes Nasim G. Salloum Pedro G. Pascutti Tha?s Souto-Padrón Robson Q. Monteiro Angela H. Lopes Igor C. Almeida 《PLoS neglected tropical diseases》2014,8(8)