全文获取类型
收费全文 | 1197篇 |
免费 | 97篇 |
出版年
2023年 | 3篇 |
2022年 | 10篇 |
2021年 | 23篇 |
2020年 | 10篇 |
2019年 | 11篇 |
2018年 | 19篇 |
2017年 | 16篇 |
2016年 | 38篇 |
2015年 | 35篇 |
2014年 | 57篇 |
2013年 | 84篇 |
2012年 | 101篇 |
2011年 | 89篇 |
2010年 | 54篇 |
2009年 | 54篇 |
2008年 | 65篇 |
2007年 | 60篇 |
2006年 | 52篇 |
2005年 | 65篇 |
2004年 | 59篇 |
2003年 | 40篇 |
2002年 | 47篇 |
2001年 | 20篇 |
2000年 | 27篇 |
1999年 | 30篇 |
1998年 | 24篇 |
1997年 | 8篇 |
1996年 | 11篇 |
1995年 | 18篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 11篇 |
1991年 | 19篇 |
1990年 | 9篇 |
1989年 | 15篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 11篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1977年 | 4篇 |
1975年 | 6篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有1294条查询结果,搜索用时 15 毫秒
1.
A knowledge-based three-dimensional model of an anti-insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL-5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL-5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL-5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epitope and 125. 相似文献
2.
Zhenbo Cao Suraj Subramaniam Neil J. Bulleid 《The Journal of biological chemistry》2014,289(9):5490-5498
Typical 2-Cys peroxiredoxins are required to remove hydrogen peroxide from several different cellular compartments. Their activity can be regulated by hyperoxidation and consequent inactivation of the active-site peroxidatic cysteine. Here we developed a simple assay to quantify the hyperoxidation of peroxiredoxins. Hyperoxidation of peroxiredoxins can only occur efficiently in the presence of a recycling system, usually involving thioredoxin and thioredoxin reductase. We demonstrate that there is a marked difference in the sensitivity of the endoplasmic reticulum-localized peroxiredoxin to hyperoxidation compared with either the cytosolic or mitochondrial enzymes. Each enzyme is equally sensitive to hyperoxidation in the presence of a robust recycling system. Our results demonstrate that peroxiredoxin IV recycling in the endoplasmic reticulum is much less efficient than in the cytosol or mitochondria, leading to the protection of peroxiredoxin IV from hyperoxidation. 相似文献
3.
Jesus Torres-Bacete Prem Kumar Sinha Motoaki Sato Gaurav Patki Mou-Chieh Kao Akemi Matsuno-Yagi Takao Yagi 《The Journal of biological chemistry》2012,287(51):42763-42772
The bacterial H+-translocating NADH:quinone oxidoreductase (NDH-1) catalyzes electron transfer from NADH to quinone coupled with proton pumping across the cytoplasmic membrane. The NuoK subunit (counterpart of the mitochondrial ND4L subunit) is one of the seven hydrophobic subunits in the membrane domain and bears three transmembrane segments (TM1–3). Two glutamic residues located in the adjacent transmembrane helices of NuoK are important for the energy coupled activity of NDH-1. In particular, mutation of the highly conserved carboxyl residue (KGlu-36 in TM2) to Ala led to a complete loss of the NDH-1 activities. Mutation of the second conserved carboxyl residue (KGlu-72 in TM3) moderately reduced the activities. To clarify the contribution of NuoK to the mechanism of proton translocation, we relocated these two conserved residues. When we shifted KGlu-36 along TM2 to positions 32, 38, 39, and 40, the mutants largely retained energy transducing NDH-1 activities. According to the recent structural information, these positions are located in the vicinity of KGlu-36, present in the same helix phase, in an immediately before and after helix turn. In an earlier study, a double mutation of two arginine residues located in a short cytoplasmic loop between TM1 and TM2 (loop-1) showed a drastic effect on energy transducing activities. Therefore, the importance of this cytosolic loop of NuoK (KArg-25, KArg-26, and KAsn-27) for the energy transducing activities was extensively studied. The probable roles of subunit NuoK in the energy transducing mechanism of NDH-1 are discussed. 相似文献
4.
Adaptation to hypoxia, defined as a condition of inadequate oxygen supply, has enabled humans to successfully colonize high altitude regions. The mechanisms attempted by organisms to cope with short-term hypoxia include increased ATP production via anaerobic respiration and stabilization of Hypoxia Inducible Factor 1α (HIF-1α). However, less is known about the means through which populations adapt to chronic hypoxia during the process of development within a life time or over generations. Here we show that signaling via the highly conserved Wnt pathway impacts the ability of Drosophila melanogaster to complete its life cycle under hypoxia. We identify this pathway through analyses of genome sequencing and gene expression of a Drosophila melanogaster population adapted over >180 generations to tolerate a concentration of 3.5–4% O2 in air. We then show that genetic activation of the Wnt canonical pathway leads to increased rates of adult eclosion in low O2. Our results indicate that a previously unsuspected major developmental pathway, Wnt, plays a significant role in hypoxia tolerance. 相似文献
5.
Water and polypeptide conformations in the gramicidin channel. A molecular dynamics study. 总被引:15,自引:14,他引:1 下载免费PDF全文
Theoretical studies of ion channels address several important questions. The mechanism of ion transport, the role of water structure, the fluctuations of the protein channel itself, and the influence of structural changes are accessible from these studies. In this paper, we have carried out a 70-ps molecular dynamics simulation on a model structure of gramicidin A with channel waters. The backbone of the protein has been analyzed with respect to the orientation of the carbonyl and the amide groups. The results are in conformity with the experimental NMR data. The structure of water and the hydrogen bonding network are also investigated. It is found that the water molecules inside the channel act as a collective chain; whereas the conformation in which all the waters are oriented with the dipoles pointing along the axis of the channel is a preferred one, others are also accessed during the dynamics simulation. A collective coordinate involving the channel waters and some of the hydrogen bonding peptide partners is required to describe the transition of waters from one configuration to the other. 相似文献
6.
Evidence that the functional beta-actin gene is single copy in most mice and is associated with 5'' sequences capable of conferring serum- and cycloheximide-dependent regulation. 总被引:8,自引:2,他引:6 下载免费PDF全文
P K Elder C L French M Subramaniam L J Schmidt M J Getz 《Molecular and cellular biology》1988,8(1):480-485
Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of this gene were shown to confer serum-inducible expression upon a heterologous reporter gene when transfected into mouse fibroblasts. Moreover, these sequences rendered reporter gene expression superinducible by a combination of serum and cycloheximide. These experiments indicate that the 5' end of the mouse beta-actin gene contains sequence elements which mediate the stimulatory effects of serum growth factors and which are responsive to both positive and negative regulators of gene expression. 相似文献
7.
Prem Kumar Dantu Sant S. Bhojwan 《Journal of plant biochemistry and biotechnology.》1992,1(2):115-118
Effect of some physical and chemical factors on in vitro shoot multiplication in Gladioius was investigated. A modified MS medium with NH4NO3 reduced to half strength, KH2PO4 replaced with 300 mg/l of NaH2PO4 2 H2O and Kl omitted completely, was found to be better than the original MS. BAP was better than either kinetin or 2iP. Of the various physical factors studied, the propagule size, light and container volume influenced the rate of shoot multiplication. On the modified medium containing 0.5 mg/l BAP in dark, the propagules bearing 20 buds showed 8-fold multiplication. 相似文献
8.
Effect of cycloheximide and growth factors on gene expression in quiescent mouse embryo fibroblasts 总被引:1,自引:0,他引:1
Gene expression in quiescent mouse embryo fibroblasts was studied by labelling the cells with [14C] amino acids and analysing the proteins by electrophoresis in polyacrylamide gradient gels containing sodium dodecyl sulfate. Cycloheximide (CH) pretreatment of the cells was found to induce the synthesis of four proteins of molecular weights 72,000, 68,000, 42,000, and 29,000. These proteins were induced by CH both in serum-arrested and serum-stimulated cells. Addition of platelet-derived growth factor to serum-arrested quiescent cells also induced the synthesis of these proteins. Addition of CH and fetal calf serum (20%) to quiescent cells resulted in a dramatic increase in the synthesis of actin and another protein of molecular weight 29,000. The 29,000-dalton protein was present in higher quantities in the nuclei of induced cells. This protein appeared to be an early protein whose synthesis was transiently induced in quiescent cells within 3 hours of addition of 20% fetal calf serum (FCS). The synthesis of this protein was virtually turned off at 5-6 hours after the addition of serum. However, if CH or a combination of CH and FCS was present, a continuous synthesis of the 29 K protein was observed. 相似文献
9.
Changes in activity levels of important enzymes of carbohydratemetabolism (and ß-amylases, sucrose synthetase, acidinvertase, acid phosphatase, glucose phosphate isomerase, aldolase,phosphofructokinase and pyruvate kinase) during seed developmentwere determined. Changes in the activities of these enzymesand their functional significance in developing seeds are described.A close correlation was found between the stage of maximum carbohydrateoxidation and the accumulation of reserve materials in the developingseeds.
1Present address: School of Agriculture and Forestry, Universityof Melbourne, Parkvilie 3052, Victoria, Australia.
2Present address: School of Botany, University of Melbourne,Parkville 3052, Victoria, Australia. (Received October 8, 1982; Accepted January 10, 1983) 相似文献
10.