全文获取类型
收费全文 | 1053篇 |
免费 | 44篇 |
国内免费 | 62篇 |
出版年
2023年 | 4篇 |
2022年 | 11篇 |
2021年 | 11篇 |
2020年 | 13篇 |
2019年 | 25篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 17篇 |
2014年 | 57篇 |
2013年 | 68篇 |
2012年 | 39篇 |
2011年 | 66篇 |
2010年 | 59篇 |
2009年 | 68篇 |
2008年 | 68篇 |
2007年 | 56篇 |
2006年 | 60篇 |
2005年 | 42篇 |
2004年 | 59篇 |
2003年 | 31篇 |
2002年 | 28篇 |
2001年 | 20篇 |
2000年 | 19篇 |
1999年 | 26篇 |
1998年 | 31篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1995年 | 16篇 |
1994年 | 18篇 |
1993年 | 11篇 |
1992年 | 21篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 14篇 |
1988年 | 6篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 23篇 |
1984年 | 2篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 9篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
排序方式: 共有1159条查询结果,搜索用时 31 毫秒
31.
32.
Jolanta Krudysz-Amblo Mark E. Jennings II Tyler Knight Dwight E. Matthews Kenneth G. Mann Saulius Butenas 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Tissue factor (TF), an in vivo initiator of blood coagulation, is a transmembrane protein and has two disulfides in the extracellular domain. The integrity of one cysteine pair, Cys186–Cys209, has been hypothesized to be essential for an allosteric “decryption” phenomenon, presumably regulating TF procoagulant function, which has been the subject of a lengthy debate. The conclusions of published studies on this subject are based on indirect evidences obtained by the use of reagents with potentially oxidizing/reducing properties.Methods
The status of disulfides in recombinant TF1–263 and natural placental TF in their non-reduced native and reduced forms was determined by mass-spectrometry. Functional assays were performed to assess TF cofactor function.Results
In native proteins, all four cysteines of the extracellular domain of TF are oxidized. Reduced TF retains factor VIIa binding capacity but completely loses the cofactor function.Conclusion
The reduction of TF disulfides (with or without alkylation) eliminates TF regulation of factor VIIa catalytic function in both membrane dependent FX activation and membrane independent synthetic substrate hydrolysis.General significance
Results of this study advance our knowledge on TF structure/function relationships. 相似文献33.
Molecular cloning,expression, and hormonal regulation of the chicken microsomal triglyceride transfer protein 总被引:1,自引:0,他引:1
N. Erwin Ivessa Edward Rehberg Bernadette Kienzle Fridolin Seif Robert Hermann Marcela Hermann Wolfgang J. Schneider David A. Gordon 《Gene》2013
During an egg-laying cycle, oviparous animals transfer massive amounts of triglycerides, the major lipid component of very low density lipoprotein (VLDL), from the liver to the developing oocytes. A major stimulus for this process is the rise in estrogen associated with the onset of an egg-laying cycle. In mammals, the microsomal triglyceride transfer protein (MTP) is required for VLDL assembly and secretion. To enable studies to determine if MTP plays a role in basal and estrogen-stimulated VLDL assembly and secretion in an oviparous vertebrate, we have cloned and sequenced the chicken MTP cDNA. This cDNA encodes a protein of 893 amino acids with an N-terminal signal sequence. The primary sequence of chicken MTP is, on average, 65% identical to that of mammalian homologs, and 23% identical to the Drosophila melanogaster protein. We have obtained a clone of chicken embryo fibroblast cells that stably express the avian MTP cDNA and show that these cells display MTP activity as measured by the transfer of a fluorescently labeled neutral lipid. As in mammals, chicken MTP is localized to the endoplasmic reticulum as revealed by indirect immunofluorescence and by the fact that its N-linked oligosaccharide moiety remains sensitive to endoglycosidase H. Endogenous, enzymatically active MTP is also expressed in an estrogen receptor-expressing chicken hepatoma cell line that secretes apolipoprotein B-containing lipoproteins. In this cell line and in vivo, the expression and activity of MTP are not influenced by estrogen. Therefore, up-regulation of MTP in the liver is not required for the increased VLDL assembly during egg production in the chicken. This indicates that MTP is not rate-limiting, even for the massive estrogen-induced secretion of VLDL accompanying an egg-laying cycle. 相似文献
34.
Xueping Chen Xiaosha Zhang Chen Li Teng Guan Huifang Shang Liying Cui Xin‐Min Li Jiming Kong 《Journal of neurochemistry》2013,124(1):45-58
A major hallmark of mutant superoxide dismutase (SOD1)‐linked familial amyotrophic lateral sclerosis is SOD1‐immunopositive inclusions found within motor neurons. The mechanism by which SOD1 becomes aggregated, however, remains unclear. In this study, we aimed to investigate the role of nitrosative stress and S‐nitrosylation of protein disulfide isomerase (PDI) in the formation of SOD1 aggregates. Our data show that with disease progression inducible nitric oxide synthase (iNOS) was up‐regulated, which generated high levels of nitric oxide (NO) and subsequently induced S‐nitrosylation of PDI in the spinal cord of mutant SOD1 transgenic mice. This was further confirmed by in vitro observation that treating SH‐SY5Y cells with NO donor S‐nitrosocysteine triggered a dose‐dependent formation of S‐nitrosylated PDI. When mutant SOD1 was over‐expressed in SH‐SY5Y cells, the iNOS expression was up‐regulated, and NO generation was consequently increased. Furthermore, both S‐nitrosylation of PDI and the formation of mutant SOD1 aggregates were detected in the cells expressing mutant SOD1G93A. Blocking NO generation with the NOS inhibitor N‐nitro‐l ‐arginine attenuated the S‐nitrosylation of PDI and inhibited the formation of mutant SOD1 aggregates. We conclude that NO‐mediated S‐nitrosylation of PDI is a contributing factor to the accumulation of mutant SOD1 aggregates in amyotrophic lateral sclerosis. 相似文献
35.
36.
37.
Compelling data supports the hypothesis that Pin1 inhibitors will be useful for the therapy of cancer: Pin1 deficient mice resist the induction of breast cancers normally evoked by expression of MMTV-driven Ras or Erb2 alleles. While Pin1 poses challenges for drug discovery, several groups have identified potent antagonists by structure based drug design, significant progress has been made designing peptidic inhibitors and a number of natural products have been found that blockade Pin1, notably epigallocatchechin gallate (EGCG), a major flavonoid in green tea. Here we critically discuss the modes of action and likely specificity of these compounds, concluding that a suitable chemical biology tool for probing the function of Pin1 has yet to be found. We conclude by outlining some open questions regarding the target validation of Pin1 and the prospects for identification of improved inhibitors in the future. 相似文献
38.
《Bioscience, biotechnology, and biochemistry》2013,77(10):2234-2239
Bacillus licheniformis L-arabinose isomerase (BLAI) with a broad pH range, high substrate specificity, and high catalytic efficiency for L-arabinose was immobilized on various supports. Eupergit C, activated-carboxymethylcellulose, CNBr-activated agarose, chitosan, and alginate were tested as supports, and Eupergit C was selected as the most effective. After determination of the optimum enzyme concentration, the effects of pH and temperature were investigated using a response surface methodology. The immobilized BLAI enzyme retained 86.4% of the activity of the free enzyme. The optimal pH for the immobilized BLAI was 8.0, and immobilization improved the optimal temperature from 50 °C (free enzyme) to a range between 55 and 65 °C. The half life improved from 2 at 50 °C to 212 h at 55 °C following immobilization. The immobilized BLAI was used for semi-continuous production of L-ribulose. After 8 batch cycles, 95.1% of the BLAI activity was retained. This simple immobilization procedure and the high stability of the final immobilized BLAI on Eupergit C provide a promising solution for large-scale production of L-ribulose from an inexpensive L-arabinose precursor. 相似文献
39.
《Bioscience, biotechnology, and biochemistry》2013,77(6):1340-1343
A variant of P450 BM3 with an F87V substitution [P450 BM3 (F87V)] is a substrate-promiscuous cytochrome P450 monooxygenase. We investigated the bioconversion of various flavonoids (favanones, chalcone, and isoflavone) by using recombinant Escherichia coli cells, which expressed the gene coding for P450 BM3 (F87V), to give their corresponding hydroxylated products. Potent antioxidative activities were observed in some of the products. 相似文献
40.
《Bioscience, biotechnology, and biochemistry》2013,77(10):2588-2591
Here we report the characterization of the type-1 isopentenyl diphosphate isomerase derived from Halobacterium sp. NRC-1. The expressed purified enzyme showed maximum isomerase activity in the presence of 1 M NaCl at 37 °C at pH 6.0. This type-1 enzyme appears to be the first for which the Co2+ ion is required for activity. 相似文献