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231.
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Zhiheng Yu Megan J. Dobro Cora L. Woodward Artem Levandovsky Cindy M. Danielson Virginie Sandrin Jiong Shi Christopher Aiken Roya Zandi Thomas J. Hope Grant J. Jensen 《Journal of molecular biology》2013,425(1):112-123
The RNA genome of retroviruses is encased within a protein capsid. To gather insight into the assembly and function of this capsid, we used electron cryotomography to image human immunodeficiency virus (HIV) and equine infectious anemia virus (EIAV) particles. While the majority of viral cores appeared closed, a variety of unclosed structures including rolled sheets, extra flaps, and cores with holes in the tip were also seen. Simulations of nonequilibrium growth of elastic sheets recapitulated each of these aberrations and further predicted the occasional presence of seams, for which tentative evidence was also found within the cryotomograms. To test the integrity of viral capsids in vivo, we observed that ~ 25% of cytoplasmic HIV complexes captured by TRIM5α had holes large enough to allow internal green fluorescent protein (GFP) molecules to escape. Together, these findings suggest that HIV assembly at least sometimes involves the union in space of two edges of a curling sheet and results in a substantial number of unclosed forms. 相似文献
233.
Neurochemical Research - Instead of the progress in the understanding of etiology of Parkinson’s disease (PD), effective methods to prevent the progression of the disease have not been... 相似文献
234.
Warshakoon NC Wu S Boyer A Kawamoto R Sheville J Renock S Xu K Pokross M Evdokimov AG Walter R Mekel M 《Bioorganic & medicinal chemistry letters》2006,16(21):5598-5601
Utilizing modeling information from a recently resolved structure of human HIF-1alpha prolyl hydroxylase (EGLN1) and structure-based design, a novel series of imidazo[1,2-a]pyridine derivatives was prepared. The activity of these compounds was determined in a human EGLN1 assay and a limited SAR was developed. 相似文献
235.
Warshakoon NC Wu S Boyer A Kawamoto R Renock S Xu K Pokross M Evdokimov AG Zhou S Winter C Walter R Mekel M 《Bioorganic & medicinal chemistry letters》2006,16(21):5687-5690
Recently resolved X-ray crystal structure of HIF-1alpha prolyl hydroxylase was used to design and develop a novel series of pyrazolopyridines as potent HIF-1alpha prolyl hydroxylase inhibitors. The activity of these compounds was determined in a human EGLN-1 assay. Structure-based design aided in optimizing the potency of the initial lead (2, IC(50) of 11 microM) to a potent (11l, 190 nM) EGLN-1 inhibitor. Several of these analogs were potent VEGF inducers in a cell-based assay. These pyrazolopyridines were also effective in stabilizing HIF-1alpha. 相似文献
236.
The stem cells in freshwater flatworms (planarian) are called neoblasts. Neoblasts are capable of proliferation and differentiation
into every cell type, including the gametes. For the investigation of the mechanisms of stem cells proliferation and differentiation
the proper evaluation of changes in the cell cycle of neoblasts in different physiological conditions of planarian is necessary.
In the present study the possibility of qualitative and quantitative characteristics of the neoblasts population were investigated
using flow cytometry. In the cell suspension prepared from planarian tissue proliferating neoblasts have been observed in
heterogenic cell population. Quantitative estimation of the cell cycle related changes of planarian stem cells system have
been performed in various physiological conditions (intact and regenerating animals) and under the influence of physical (ionizing
radiation) and chemical (melatonin and colchicine) factors. The modified protocol for planarian stem cells isolation proved
to be effective and reproducible and can be recommended for flow cytometry analyses of human and animal proliferating cells. 相似文献
237.
Lu H Efremov AK Bookwalter CS Krementsova EB Driver JW Trybus KM Diehl MR 《The Journal of biological chemistry》2012,287(33):27753-27761
Characterization of the collective behaviors of different classes of processive motor proteins has become increasingly important to understand various intracellular trafficking and transport processes. This work examines the dynamics of structurally-defined motor complexes containing two myosin Va (myoVa) motors that are linked together via a molecular scaffold formed from a single duplex of DNA. Dynamic changes in the filament-bound configuration of these complexes due to motor binding, stepping, and detachment were monitored by tracking the positions of different color quantum dots that report the position of one head of each myoVa motor on actin. As in studies of multiple kinesins, the run lengths produced by two myosins are only slightly larger than those of single motor molecules. This suggests that internal strain within the complexes, due to asynchronous motor stepping and the resultant stretching of motor linkages, yields net negative cooperative behaviors. In contrast to multiple kinesins, multiple myosin complexes move with appreciably lower velocities than a single-myosin molecule. Although similar trends are predicted by a discrete state stochastic model of collective motor dynamics, these analyses also suggest that multiple myosin velocities and run lengths depend on both the compliance and the effective size of their cargo. Moreover, it is proposed that this unique collective behavior occurs because the large step size and relatively small stalling force of myoVa leads to a high sensitivity of motor stepping rates to strain. 相似文献
238.
Evdokimov AG Mekel M Hutchings K Narasimhan L Holler T McGrath T Beattie B Fauman E Yan C Heaslet H Walter R Finzel B Ohren J McConnell P Braden T Sun F Spessard C Banotai C Al-Kassim L Ma W Wengender P Kole D Garceau N Toogood P Liu J 《Journal of structural biology》2008,162(1):152-169
In this article, we describe for the first time the high-resolution crystal structure of a phenylalanine tRNA synthetase from the pathogenic bacterium Staphylococcus haemolyticus. We demonstrate the subtle yet important structural differences between this enzyme and the previously described Thermus thermophilus ortholog. We also explain the structure-activity relationship of several recently reported inhibitors. The native enzyme crystals were of poor quality--they only diffracted X-rays to 3-5A resolution. Therefore, we have executed a rational surface mutagenesis strategy that has yielded crystals of this 2300-amino acid multidomain protein, diffracting to 2A or better. This methodology is discussed and contrasted with the more traditional domain truncation approach. 相似文献
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240.