全文获取类型
收费全文 | 1058篇 |
免费 | 97篇 |
出版年
2023年 | 5篇 |
2022年 | 13篇 |
2021年 | 25篇 |
2020年 | 13篇 |
2019年 | 23篇 |
2018年 | 27篇 |
2017年 | 26篇 |
2016年 | 31篇 |
2015年 | 44篇 |
2014年 | 60篇 |
2013年 | 74篇 |
2012年 | 69篇 |
2011年 | 84篇 |
2010年 | 41篇 |
2009年 | 57篇 |
2008年 | 65篇 |
2007年 | 71篇 |
2006年 | 74篇 |
2005年 | 69篇 |
2004年 | 52篇 |
2003年 | 51篇 |
2002年 | 69篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 15篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 12篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有1155条查询结果,搜索用时 46 毫秒
991.
Ding F Sharma S Chalasani P Demidov VV Broude NE Dokholyan NV 《RNA (New York, N.Y.)》2008,14(6):1164-1173
RNA molecules with novel functions have revived interest in the accurate prediction of RNA three-dimensional (3D) structure and folding dynamics. However, existing methods are inefficient in automated 3D structure prediction. Here, we report a robust computational approach for rapid folding of RNA molecules. We develop a simplified RNA model for discrete molecular dynamics (DMD) simulations, incorporating base-pairing and base-stacking interactions. We demonstrate correct folding of 150 structurally diverse RNA sequences. The majority of DMD-predicted 3D structures have <4 A deviations from experimental structures. The secondary structures corresponding to the predicted 3D structures consist of 94% native base-pair interactions. Folding thermodynamics and kinetics of tRNA(Phe), pseudoknots, and mRNA fragments in DMD simulations are in agreement with previous experimental findings. Folding of RNA molecules features transient, non-native conformations, suggesting non-hierarchical RNA folding. Our method allows rapid conformational sampling of RNA folding, with computational time increasing linearly with RNA length. We envision this approach as a promising tool for RNA structural and functional analyses. 相似文献
992.
Evaluating Burkholderia pseudomallei Bip proteins as vaccines and Bip antibodies as detection agents 总被引:1,自引:0,他引:1
Druar C Yu F Barnes JL Okinaka RT Chantratita N Beg S Stratilo CW Olive AJ Soltes G Russell ML Limmathurotsakul D Norton RE Ni SX Picking WD Jackson PJ Stewart DI Tsvetnitsky V Picking WL Cherwonogrodzky JW Ketheesan N Peacock SJ Wiersma EJ 《FEMS immunology and medical microbiology》2008,52(1):78-87
Burkholderia pseudomallei is a biothreat agent and an important natural pathogen, causing melioidosis in humans and animals. A type III secretion system (TTSS-3) has been shown to be critical for virulence. Because TTSS components from other pathogens have been used successfully as diagnostic agents and as experimental vaccines, it was investigated whether this was the case for BipB, BipC and BipD, components of B. pseudomallei's TTSS-3. The sequences of BipB, BipC and BipD were found to be highly conserved among B. pseudomallei and B. mallei isolates. A collection of monoclonal antibodies (mAbs) specific for each Bip protein was obtained. Most recognized both native and denatured Bip protein. Burkholderia pseudomallei or B. mallei did not express detectable BipB or BipD under the growth conditions used. However, anti-BipD mAbs did recognize the TTSS needle structures of a Shigella strain engineered to express BipD. The authors did not find that BipB, BipC or BipD are protective antigens because vaccination of mice with any single protein did not result in protection against experimental melioidosis. Enzyme-linked immunosorbent assay (ELISA) studies showed that human melioidosis patients had antibodies to BipB and BipD. However, these ELISAs had low diagnostic accuracy in endemic regions, possibly due to previous patient exposure to B. pseudomallei. 相似文献
993.
Guerreiro AR Korkhov V Mijangos I Piletska EV Rodins J Turner AP Piletsky SA 《Biosensors & bioelectronics》2008,23(7):1189-1194
A set of polymers was imprinted with (-)-ephedrine using UV initiation, under the influence of a constant external magnetic field with intensities ranging from 0 to 1.55 T. Synthesised materials were characterised by X-ray crystallography, infrared spectroscopy, swelling and surface area. Recognition properties were assessed by the ability to discriminate between (+) and (-)-ephedrine and by Scatchard analyses on chromatographic mode. It was shown that polymer morphology and recognition properties are affected by the magnetic field. This resulted in considerable improvements in the chromatographic resolution of ephedrine enantiomers by materials synthesised under the influence of magnetic field. Apparently the magnetic field improved the ordering of the polymer structure and facilitated the formation of more uniform imprinting sites. 相似文献
994.
995.
Background
Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status. 相似文献996.
Fujimoto YK Terbush RN Patsalo V Green DF 《Protein science : a publication of the Protein Society》2008,17(11):2008-2014
The prokaryotic lectin cyanovirin-N (CV-N) is a potent inhibitor of HIV envelope-mediated cell entry, and thus is a leading candidate among a new class of potential anti-HIV microbicides. The activity of CV-N is a result of interactions with the D1 arm of high-mannose oligosaccharides on the viral glycoprotein gp120. Here, we present computationally refined models of CV-N recognition of the di- and trisaccharides that represent the terminal three sugars of the D1 arm by each CV-N binding site. These models complement existing structural data, both from NMR spectroscopy and X-ray crystallography. When used with a molecular dynamics/continuum electrostatic (MD/PBSA) approach to compute binding free energies, these models explain the relative affinity of each site for the two saccharides. This work presents the first validation of the application of continuum electrostatic models to carbohydrate-protein association. Taken as a whole, the results both provide models of CV-N sugar recognition and demonstrate the utility of these computational methods for the study of carbohydrate-binding proteins. 相似文献
997.
Klaus-Peter Koepfli Budsabong Kanchanasaka Hiroshi Sasaki Hélène Jacques Kristina D. Y. Louie Toanvong Hoai Nguyen Xuan Dang Eli Geffen Arno Gutleb Sung-yong Han Thrine M. Heggberget Lionel LaFontaine Hang Lee Roland Melisch Jordi Ruiz-Olmo Margarida Santos-Reis Vadim E. Sidorovich Michael Stubbe Robert K. Wayne 《Conservation Genetics》2008,9(6):1589-1604
Four species of otters (Mustelidae, Lutrinae) occur in Southeast Asia and are considered to be of conservation concern: Aonyx cinerea (Asian small-clawed otter), Lutra lutra (Eurasian otter), Lutra sumatrana (Hairy-nosed otter), and Lutrogale perspicillata (Smooth-coated otter). Among these, L. sumatrana is endemic to the region, yet little is known about its biology, and the precise distribution of all four species in Southeast
Asia is not well known. Furthermore, the taxonomy and systematics of L. sumatrana and L. perspicillata have been the subject of controversy, which has implications for the legal protection and for conservation programs of these
taxa. To resolve these controversies, we used a multigene data set comprised of segments from 13 nuclear and 5 mitochondrial
loci (11,180 nucleotides) to evaluate the phylogenetic relationships of Asian Old World otters. Phylogenies were also estimated
using two mitochondrial loci (1,832 nucleotides) obtained from two or more individuals of the four Southeast Asian species.
The results from maximum parsimony, maximum likelihood and Bayesian inference showed that L. sumatrana and L. lutra are sister taxa, whereas L. perspicillata is sister to A. cinerea. Furthermore, the results from the two-mitochondrial gene analyses indicate that L. sumatrana is reciprocally monophyletic with respect to L. lutra, supporting the specific validity of the former taxon. Signs such as tracks and feces are often used in field surveys to
provide information on the distribution and abundance of otters, but the accuracy of these methods may be compromised when
several closely related species occur sympatrically. Therefore, the two-gene data set was used to develop a provisional set
of diagnostic nucleotides that can be potentially used to identify the four species of Southeast Asian otters from noninvasively
collected biological samples, such as feces.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
998.
Polypyrimidine tract binding protein (PTB) is known to silence the splicing of many alternative exons. However, exons repressed by PTB are affected by other RNA regulatory elements and proteins. This makes it difficult to dissect the structure of the pre-mRNP complexes that silence splicing, and to understand the role of PTB in this process. We determined the minimal requirements for PTB-mediated splicing repression. We find that the minimal sequence for high affinity binding by PTB is relatively large, containing multiple polypyrimidine elements. Analytical ultracentrifugation and proteolysis mapping of RNA cross-links on the PTB protein indicate that most PTB exists as a monomer, and that a polypyrimidine element extends across multiple PTB domains. The high affinity site is bound initially by a PTB monomer and at higher concentrations by additional PTB molecules. Significantly, this site is not sufficient for splicing repression when placed in the 3' splice site of a strong test exon. Efficient repression requires a second binding site within the exon itself or downstream from it. This second site enhances formation of a multimeric PTB complex, even if it does not bind well to PTB on its own. These experiments show that PTB can be sufficient to repress splicing of an otherwise constitutive exon, without binding sites for additional regulatory proteins and without competing with U2AF binding. The minimal complex mediating splicing repression by PTB requires two binding sites bound by an oligomeric PTB complex. 相似文献
999.
For over 30 years, photoreceptors have been an outstanding model system for elucidating basic principles in sensory transduction and G protein signaling. Recently, photoreceptors have become an equally attractive model for studying many facets of neuronal cell biology. The primary goal of this review is to illustrate this rapidly growing trend. We will highlight the areas of active research in photoreceptor biology that reveal how different specialized compartments of the cell cooperate in fulfilling its overall function: converting photon absorption into changes in neurotransmitter release. The same trend brings us closer to understanding how defects in photoreceptor signaling can lead to cell death and retinal degeneration. 相似文献
1000.
Insulin stimulates the halting, tethering, and fusion of mobile GLUT4 vesicles in rat adipose cells 总被引:11,自引:0,他引:11
Lizunov VA Matsumoto H Zimmerberg J Cushman SW Frolov VA 《The Journal of cell biology》2005,169(3):481-489
Glucose transport in adipose cells is regulated by changing the distribution of glucose transporter 4 (GLUT4) between the cell interior and the plasma membrane (PM). Insulin shifts this distribution by augmenting the rate of exocytosis of specialized GLUT4 vesicles. We applied time-lapse total internal reflection fluorescence microscopy to dissect intermediates of this GLUT4 translocation in rat adipose cells in primary culture. Without insulin, GLUT4 vesicles rapidly moved along a microtubule network covering the entire PM, periodically stopping, most often just briefly, by loosely tethering to the PM. Insulin halted this traffic by tightly tethering vesicles to the PM where they formed clusters and slowly fused to the PM. This slow release of GLUT4 determined the overall increase of the PM GLUT4. Thus, insulin initially recruits GLUT4 sequestered in mobile vesicles near the PM. It is likely that the primary mechanism of insulin action in GLUT4 translocation is to stimulate tethering and fusion of trafficking vesicles to specific fusion sites in the PM. 相似文献