全文获取类型
收费全文 | 275篇 |
免费 | 15篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 6篇 |
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 14篇 |
2014年 | 17篇 |
2013年 | 16篇 |
2012年 | 17篇 |
2011年 | 25篇 |
2010年 | 10篇 |
2009年 | 8篇 |
2008年 | 11篇 |
2007年 | 9篇 |
2006年 | 10篇 |
2005年 | 6篇 |
2004年 | 8篇 |
2003年 | 7篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 12篇 |
1999年 | 7篇 |
1998年 | 11篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 1篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有290条查询结果,搜索用时 203 毫秒
11.
Gagneux P Amess B Diaz S Moore S Patel T Dillmann W Parekh R Varki A 《American journal of physical anthropology》2001,115(2):99-109
Most blood plasma proteins are glycosylated. These glycoproteins typically carry sialic acid-bearing sugar chains, which can modify the observed molecular weights and isoelectric points of those proteins during electrophoretic analyses. To explore changes in protein expression and glycosylation that occurred during great ape and human evolution, we subjected multiple blood plasma samples from all these species to high-resolution proteomic analysis. We found very few species-specific differences, indicating a remarkable degree of conservation of plasma protein expression and glycosylation during approximately 12 million years of evolution. A few lineage-specific differences in protein migration were noted among the great apes. The only obvious differences between humans and all great apes were an apparent decrease in transthyretin (prealbumin) and a change in haptoglobin isoforms (the latter was predictable from prior genetic studies). Quantitative studies of transthyretin in samples of blood plasma (synthesized primarily by the liver) and of cerebrospinal fluid (synthesized locally by the choroid plexus of the brain) confirmed approximately 2-fold higher levels in chimpanzees compared to humans. Since transthyretin binds thyroid hormones, we next compared plasma thyroid hormone parameters between humans and chimpanzees. The results indicate significant differences in the status of thyroid hormone metabolism, which represent the first known endocrine difference between these species. Notably, thyroid hormones are known to play major roles in the development, differentiation, and metabolism of many organs and tissues, including the brain and the cranium. Also, transthyretin is known to be the major carrier of thyroid hormone in the cerebrospinal fluid, likely regulating delivery of this hormone to the brain. A potential secondary difference in retinoid (vitamin A) metabolism is also noted. The implications of these findings for explaining unique features of human evolution are discussed. 相似文献
12.
B cells activated by lipopolysaccharide,but not by anti-Ig and anti-CD40 antibody,induce anergy in CD8+ T cells: role of TGF-beta 1 总被引:1,自引:0,他引:1
Parekh VV Prasad DV Banerjee PP Joshi BN Kumar A Mishra GC 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):5897-5911
B cells recognize Ag through their surface IgRs and present it in the context of MHC class II molecules to CD4(+) T cells. Recent evidence indicates that B cells also present exogenous Ags in the context of MHC class I to CD8(+) T cells and thus may play an important role in the modulation of CTL responses. However, in this regard, conflicting reports are available. One group of studies suggests that the interaction between B cells and CD8(+) T cells leads to the activation of the T cells, whereas other studies propose that it induces T cell tolerance. For discerning this dichotomy, we used B cells that were activated with either LPS or anti-Ig plus anti-CD40 Ab, which mimic the T-independent and T-dependent modes of B cell activation, respectively, to provide accessory signals to resting CD8(+) T cells. Our results show that, in comparison with anti-Ig plus anti-CD40 Ab-activated B cells, the LPS-activated B cells (LPS-B) failed to induce significant levels of proliferation, cytokine secretion, and cytotoxic ability of CD8(+) T cells. This hyporesponsiveness of CD8(+) T cells activated with LPS-B was significantly rescued by anti-TGF-beta1 Ab. Moreover, it was found that such hyporesponsive CD8(+) T cells activated with LPS-B had entered a state of anergy. Furthermore, LPS-B expresses a significantly higher level of TGF-beta1 on the surface, which caused the observed hyporesponsiveness of CD8(+) T cells. Therefore, this study, for the first time, provides a novel mechanism of B cell surface TGF-beta1-mediated hyporesponsiveness leading to anergy of CD8(+) T cells. 相似文献
13.
Prasad DV Parekh VV Joshi BN Banerjee PP Parab PB Chattopadhyay S Kumar A Mishra GC 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(4):1801-1809
In an earlier report, we had shown a 150-kDa protein termed as M150, isolated from the surface of activated macrophages, to possess costimulatory activity for CD4(+) T cells. Significantly, this protein was found to specifically elicit Th1 responses. In this study, we characterize M150, which belongs to a unique subset of the lysosome-associated membrane protein-1 glycoprotein. Interestingly, the costimulatory activity of M150 depends on its posttranslational modification, which has a distinct glycosylation pattern restricted to macrophages. Furthermore, it has been demonstrated that in addition to stimulating Th1-specific responses, M150 is also capable of driving differentiation of naive CD4(+) T cells into the Th1 subset. This altered posttranslational modification of housekeeping protein appears to represent a novel pathway by which APCs can additionally regulate T cell responses. 相似文献
14.
Improvement of microbial strains and fermentation processes 总被引:20,自引:0,他引:20
Improvement of microbial strains for the over-production of industrial products has been the hallmark of all commercial fermentation
processes. Conventionally, strain improvement has been achieved through mutation, selection, or genetic recombination. Over-production
of primary or secondary metabolites is a complex process, and successful development of improved strains requires a knowledge
of physiology, pathway regulation and control, and the design of creative screening procedures. In addition, it requires mastery
of the fermentation process for each new strain, as well as sound engineering know-how for media-optimization and the fine-tuning
of process conditions. This review focuses on the various options that may be employed to improve microbial strains and addresses
the complex problems of screening, the tools and technology behind the selection of targeted organisms, and the importance
of process optimization. Furthermore, this review discusses new and emerging technologies and designing optimized media for
tracking mutants with enhanced productivity or other desired attributes.
Received: 7 February 2000 / Received revision: 2 May 2000 / Accepted: 2 May 2000 相似文献
15.
Fong NM Jensen TC Shah AS Parekh NN Saltiel AR Brady MJ 《The Journal of biological chemistry》2000,275(45):35034-35039
The activation of protein phosphastase-1 (PP1) by insulin plays a critical role in the regulation of glycogen metabolism. PTG is a PP1 glycogen-targeting protein, which also binds the PP1 substrates glycogen synthase, glycogen phosphorylase, and phosphorylase kinase (Printen, J. A., Brady, M. J., and Saltiel, A. R. (1997) Science 275, 1475-1478). Through a combination of deletion analysis and site-directed mutagenesis, the regions on PTG responsible for binding PP1 and its substrates have been delineated. Mutagenesis of Val-62 and Phe-64 in the highly conserved (K/R)VXF PP1-binding motif to alanine was sufficient to ablate PP1 binding to PTG. Phosphorylase kinase, glycogen synthase, and phosphorylase binding all mapped to the same C-terminal region of PTG. Mutagenesis of Asp-225 and Glu-228 to alanine completely blocked the interaction between PTG and these three enzymes, without affecting PP1 binding. Disruption of either PP1 or substrate binding to PTG blocked the stimulation of PP1 activity in vitro against phosphorylase, indicating that both binding sites may be important in PTG action. Transient overexpression of wild-type PTG in Chinese hamster ovary cells overexpressing the insulin receptor caused a 50-fold increase in glycogen levels. Expression of PTG mutants that do not bind PP1 had no effect on glycogen accumulation, indicating that PP1 targeting is essential for PTG function. Likewise, expression of the PTG mutants that do not bind PP1 substrates did not increase glycogen levels, indicating that PP1 targeting glycogen is not sufficient for the metabolic effects of PTG. These results cumulatively demonstrate that PTG serves as a molecular scaffold, allowing PP1 to recognize its substrates at the glycogen particle. 相似文献
16.
Leader peptide efficiency correlates with signal recognition particle dependence in Saccharomyces cerevisiae 总被引:1,自引:0,他引:1
Secretion of bovine pancreatic trypsin inhibitor (BPTI) in Saccharomyces cerevisiae was examined with four different leader peptides: the invertase signal peptide, the mfalpha1 signal peptide, a synthetic signal peptide, and a synthetic pre pro leader. BPTI secretion from a low-copy CEN plasmid varies from 1.8 to 10.4 microgram/mL among these constructs. Secretion titers correlate with dependence on signal recognition particle (SRP), with greatest secretion from the most SRP-dependent construct. Examination of co- vs post-translational translocation pathways and overall translocation efficiency by ubiquitin translocation assay (UTA) does not provide insight into the variation in BPTI secretion efficiency, perhaps due to alteration in translocation kinetics from the additional polypeptide fusion required by the assay. BPTI translocation efficiency (as measured by UTA) is found to drop markedly upon depletion of Srp54p, prior to any observable growth defect. Subsequent to stress response induction and the onset of slow growth (15-h doubling time), BPTI translocation efficiency recovers to the level observed prior to SRP depletion. 相似文献
17.
P. Gyaneshwar G. Naresh Kumar L.J. Parekh 《World journal of microbiology & biotechnology》1998,14(5):669-673
Native microflora present in the alkaline vertisols and two phosphate-solubilizing bacteria (PSB) isolated from soil using conventional screening media could not release phosphorus from alkaline Indian vertisol soils supplemented with carbon and nitrogen sources. The two PSBs could solubilize both rock phosphate and di-calcium phosphate in unbuffered media but failed to solubilize rock phosphate in buffered media. The organic acids secreted by these PSBs were 20–50 times less than that required to solubilize phosphorus from alkaline soil. 相似文献
18.
19.
Development of a cost-effective glucose-corn steep medium for production of butanol by Clostridium beijerinckii 总被引:1,自引:0,他引:1
M Parekh J Formanek H P Blaschek 《Journal of industrial microbiology & biotechnology》1998,21(4-5):187-191
Corn steep water (CSW) medium (1.6% solids plus 6% glucose) was evaluated for growth and butanol production by Clostridium beijerinckii NCIMB 8052 wild-type and hyper-amylolytic, hyper-butanol-producing mutant strain BA101. CSW alone was not a suitable substrate,
whereas addition of glucose supported growth and butanol production by both strains. In a batch-scale fermentation using an
optimized 6% glucose-1.6% solids CSW medium, C. beijerinckii NCIMB 8052 and strain BA101 produced 10.7 g L−1 and 14.5 g L−1 of butanol, respectively. The total solvents (acetone, butanol, and ethanol) produced by C. beijerinckii NCIMB 8052 and strain BA101 were 14 g L−1 and 20 g L−1, respectively. Initial fermentation in small-scale flasks containing 6% maltodextrin-1.6% solids concentration CSW medium
resulted in 6 g L−1 and 12.6 g L−1 of butanol production by C. beijerinckii NCIMB 8052 and strain BA101, respectively. CSW can serve as an economic source of nitrogen, vitamins, amino acids, minerals,
and other nutrients. Thus, it is feasible to use 6% glucose-1.6% solids CSW medium in place of semi-defined P2 medium.
Received 9 February 1998/ Accepted in revised form 1 September 1998 相似文献
20.
Jignesh M. Parekh Rajendrasinh N. Vaghela Dipen K. Sutariya Mallika Sanyal Manish Yadav Pranav S. Shrivastav 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(24):2217-2225
A sensitive, selective and high throughput liquid chromatography tandem mass spectrometry (LC–ESI-MS/MS) method has been developed for the determination of teriflunomide, an active metabolite of leflunomide in human plasma. Plasma samples were prepared by liquid–liquid extraction of teriflunomide and valsartan as internal standard (IS) in ethyl acetate from 200 μL human plasma. The chromatographic separation was achieved on an Inertsil ODS-3 C18 (50 mm × 4.6 mm, 3 μm) analytical column using isocratic mobile phase, consisting of 20 mM ammonium acetate–methanol (25:75, v/v), at a flow-rate of 0.8 mL/min. The precursor → product ion transition for teriflunomide (m/z 269.0 → 82.0) and IS (m/z 434.1 → 350.3) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) and negative ion mode. The method was validated over a wide dynamic concentration range of 10.1–4001 ng/mL. Matrix effect was assessed by post-column infusion experiment and the mean process efficiency were 91.7% and 88.2% for teriflunomide and IS respectively. The method was rugged and rapid with a total run time of 2.0 min and is applied to a bioequivalence study of 20 mg leflunomide (test and reference) tablet formulation in 12 healthy Indian male subjects under fasting condition. 相似文献