全文获取类型
收费全文 | 824篇 |
免费 | 40篇 |
国内免费 | 1篇 |
专业分类
865篇 |
出版年
2023年 | 7篇 |
2022年 | 21篇 |
2021年 | 23篇 |
2020年 | 9篇 |
2019年 | 19篇 |
2018年 | 28篇 |
2017年 | 22篇 |
2016年 | 33篇 |
2015年 | 42篇 |
2014年 | 62篇 |
2013年 | 55篇 |
2012年 | 71篇 |
2011年 | 74篇 |
2010年 | 50篇 |
2009年 | 36篇 |
2008年 | 32篇 |
2007年 | 46篇 |
2006年 | 26篇 |
2005年 | 26篇 |
2004年 | 24篇 |
2003年 | 21篇 |
2002年 | 23篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 3篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1994年 | 5篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1976年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 4篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有865条查询结果,搜索用时 15 毫秒
141.
Introduction
Bone morphogenetic proteins (BMPs) are critical growth factors in the osteogenic differentiation of progenitor cells during development in embryos and fracture repair in adults. Although recombinant BMPs are in use clinically, their clinical efficiency needs to be improved. The biological activities of BMPs are naturally regulated by extracellular binding proteins. The specific hypotheses tested in this study were as follows: the BMP inhibitor chordin is produced endogenously during the osteogenic differentiation of human mesenchymal stem cells (MSCs); and blockade of the activity of the BMP inhibitor increases the rate of osteogenic differentiation of human MSCs in vitro.Methods
Human MSCs were derived from bone marrow from an iliac crest aspirate and from patients undergoing hip hemiarthroplasty. The MSCs were induced down the osteogenic pathway using standard osteogenic differentiation media, and expressions of BMP-2 and chordin were determined by gene expression analysis. During osteogenic differentiation, chordin knockdown was induced using RNA interference. Osteogenic differentiation was assessed by measuring the expression of alkaline phosphatase and calcium deposition. The differences in expression of osteogenic makers between groups were compared by analysis of variance, followed by Gabriel post hoc test.Results
We demonstrate the expression of BMP-2 and chordin in human MSCs during osteogenic differentiation. Knockdown of chordin by RNA interference in vitro resulted in a significant increase in the expression of the osteogenic marker alkaline phosphatase and the deposition of extracellular mineral, in response to osteogenic stimulation.Conclusion
We conclude that endogenously produced chordin constrains the osteogenic differentiation of human MSCs. The targeting of BMP inhibitors, such as chordin, may provide a novel strategy for enhancing bone regeneration. 相似文献142.
Extensive research has provided ample evidences suggesting that protein folding in the cell is a co-translational process1-5. However, the exact pathway that polypeptide chain follows during co-translational folding to achieve its functional form is still an enigma. In order to understand this process and to determine the exact conformation of the co-translational folding intermediates, it is essential to develop techniques that allow the isolation of RNCs carrying nascent chains of predetermined sizes to allow their further structural analysis.SecM (secretion monitor) is a 170 amino acid E. coli protein that regulates expression of the downstream SecA (secretion driving) ATPase in the secM-secA operon6. Nakatogawa and Ito originally found that a 17 amino acid long sequence (150-FSTPVWISQAQGIRAGP-166) in the C-terminal region of the SecM protein is sufficient and necessary to cause stalling of SecM elongation at Gly165, thereby producing peptidyl-glycyl-tRNA stably bound to the ribosomal P-site7-9. More importantly, it was found that this 17 amino acid long sequence can be fused to the C-terminus of virtually any full-length and/or truncated protein thus allowing the production of RNCs carrying nascent chains of predetermined sizes7. Thus, when fused or inserted into the target protein, SecM stalling sequence produces arrest of the polypeptide chain elongation and generates stable RNCs both in vivo in E. coli cells and in vitro in a cell-free system. Sucrose gradient centrifugation is further utilized to isolate RNCs.The isolated RNCs can be used to analyze structural and functional features of the co-translational folding intermediates. Recently, this technique has been successfully used to gain insights into the structure of several ribosome bound nascent chains10,11. Here we describe the isolation of bovine Gamma-B Crystallin RNCs fused to SecM and generated in an in vitro translation system. 相似文献
143.
Chaudhuri K Das S Bandyopadhyay M Zalar A Kollmann A Jha S Tepfer D 《Transgenic research》2009,18(1):121-134
Plant secondary metabolites, including pharmaceuticals, flavorings and aromas, are often produced in response to stress. We
used chemical inducers of the pathogen defense response (jasmonic acid, salicylate, killed fungi, oligosaccharides and the
fungal elicitor protein, cryptogein) to increase metabolite and biomass production in transformed root cultures of the medicinal
plant, Withania somnifera, and the weed, Convolvulus sepium. In an effort to genetically mimic the observed effects of cryptogein, we employed Agrobacterium rhizogenes to insert a synthetic gene encoding cryptogein into the roots of C. sepium, W. somnifera and Tylophora tanakae. This genetic transformation was associated with stimulation in both secondary metabolite production and growth in the first
two species, and in growth in the third. In whole plants of Convolvulus arvensis and Arabidopsis thaliana, transformation with the cryptogein gene led, respectively, to increases in the calystegines and certain flavonoids. A similar
transgenic mimicry of pathogen attack was previously employed to stimulate resistance to the pathogen and abiotic stress.
In the present study of biochemical phenotype, we show that transgenic mimicry is correlated with increased secondary metabolite
production in transformed root cultures and whole plants. We propose that natural transformation with genes encoding the production
of microbial elicitors could influence interactions between plants and other organisms. 相似文献
144.
Veerendra Kumar Verma Avinash Pandey Anjani Kumar Jha S. V. Ngachan 《Physiology and Molecular Biology of Plants》2017,23(4):911-924
Chayote or chow–chow is an underutilized cucurbit vegetable crop, widely cultivated by farmers in the backyards and Jhum lands for its tender leaves, fruits and tuberous root. In order to initiate crop improvement program in this crop, the present study was undertaken to assess the genetic variations in the 74 chow–chow landraces collected from the North Eastern Hill region of India. Wide variations for fruit colors, fruit length (6.5–21.5 cm), fruit width (4.2–10.7 cm), fruit weight (60–560 g), vitamin-C (2.6–13.8 mg/100 g), reducing sugar (0.18–2.77%), total sugar (1.09–2.94%) and phenol content (0.17–3.85 mg/100 g FW) were recorded among the landraces. All the landraces were also characterized using random amplified polymorphic DNA (RAPD) and inter simple sequence repeat (ISSR) markers. In RAPD analyses, out of 28 primers a total of 198 reproducible amplicons were formed at an average of 7.01 per primer and an overall polymorphism of 88.38%. Eight fragments were specific to landraces with light green fruits. Four fragments were observed to be specific to RCSC-22 (dark green fruits) and another four specific to a RCSC-30 (pale yellow fruits). Out of 30 ISSR, only 5 primers generated a total of 32 reproducible amplicons with an average of 6.4 per primer and overall polymorphism of 62.5%. The pair wise similarity coefficient values ranged from 0.55 to 0.96. The grouping of landraces in cluster analysis was found to be independent of their respective geographic locations. The cuttings of suckers and shoot top (2 months old) treated with indole-3-butyric acid (200 mg l?1) provide an alternative for the conservation of the diverse genetic materials to the researchers. 相似文献
145.
A halotolerant plant-growth-promoting rhizobacteria (PGPR) can ameliorate salt stress in associated plants by various mechanisms. Therefore, the present study aimed to characterize a PGPR Klebsiella sp. SBP-8 for its ability to tolerate salt stress and to study the mechanism of PGPR-mediated mitigation of salt stress in the wheat plant. The abiotic stressors result in multiple changes in the fatty acid composition of Klebsiella sp. SBP-8, helping the membrane to keep its integrity, fluidity, and function for its growth under salt (NaCl) stress conditions. The changes in fatty acid composition of test organism were analyzed by fatty acid methyl ester (FAME) analysis under varying saline conditions. The spectroscopy (GC-MS) profile of cell extract at different salt concentrations was comprised of hydrocarbons, and fatty alcohols with varying carbon chain length. Inoculation of Klebsiella sp. SBP-8 to wheat seedling showed increase in proline, total soluble sugar, and total protein content of treated plants. Bacterial inoculation also decreased the concentration of salinity-induced malondialdehyde (MDA) content. In addition, bacterial inoculation also increased the various antioxidative enzymes like superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX) in treated plants. It is likely that bacterial inoculation alleviated the salt stress to wheat plant by co-ordination of antioxidative machinery, and improvement in osmolyte contents. Therefore, the present study suggests that bacterial-inoculated wheat plants were able to cope better with salt stress than uninoculated control, therefore it can serve as a promising bio-inoculant for enhancing the growth of wheat like cereal crops under saline stress. 相似文献
146.
147.
Singh Rajnish Prakash Jha Prameela Jha Prabhat Nath 《Journal of Plant Growth Regulation》2017,36(3):783-798
Journal of Plant Growth Regulation - Bacteria residing in the rhizosphere and capable of host plant growth stimulation (PGPR) through ACC-deaminase activity can ameliorate various biotic- and... 相似文献
148.
Kumar Srivastava B Soni R Patel JZ Jha S Shedage SA Gandhi N Sairam KV Pawar V Sadhwani N Mitra P Jain MR Patel PR 《Bioorganic & medicinal chemistry letters》2008,18(14):3882-3886
Facile synthesis of biaryl pyrazole sulfonamide derivative of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxylic acid piperidin-1-ylamide (SR141716, 1) and an investigation of the effect of replacement of the –CO group in the compound 1 by the –SO2 group in the aminopiperidine region is reported. Primary ex-vivo pharmacological testing and in vitro screening of sulfonamide derivative 2 showed the loss of CB1 receptor antagonism. 相似文献
149.
The neuronal dynamin1 functions in the release of synaptic vesicles by orchestrating the process of GTPase-dependent membrane fission. Dynamin1 associates with the plasma membrane–localized phosphatidylinositol-4,5-bisphosphate (PIP2) through the centrally located pleckstrin homology domain (PHD). The PHD is dispensable as fission (in model membranes) can be managed, even when the PHD-PIP2 interaction is replaced by a generic polyhistidine- or polylysine-lipid interaction. However, the absence of the PHD renders a dramatic dampening of the rate of fission. These observations suggest that the PHD-PIP2–containing membrane interaction could have evolved to expedite fission to fulfill the requirement of rapid kinetics of synaptic vesicle recycling. Here, we use a suite of multiscale modeling approaches to explore PHD–membrane interactions. Our results reveal that 1) the binding of PHD to PIP2-containing membranes modulates the lipids toward fission-favoring conformations and softens the membrane, and 2) PHD associates with membrane in multiple orientations using variable loops as pivots. We identify a new loop (VL4), which acts as an auxiliary pivot and modulates the orientation flexibility of PHD on the membrane—a mechanism that we believe may be important for high-fidelity dynamin collar assembly. Together, these insights provide a molecular-level understanding of the catalytic role of PHD in dynamin-mediated membrane fission. 相似文献
150.