全文获取类型
收费全文 | 163篇 |
免费 | 14篇 |
专业分类
177篇 |
出版年
2023年 | 1篇 |
2021年 | 3篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 10篇 |
2013年 | 13篇 |
2012年 | 18篇 |
2011年 | 12篇 |
2010年 | 11篇 |
2009年 | 2篇 |
2008年 | 8篇 |
2007年 | 11篇 |
2006年 | 12篇 |
2005年 | 7篇 |
2004年 | 8篇 |
2003年 | 9篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有177条查询结果,搜索用时 15 毫秒
91.
Iyer VR 《Genome biology》2003,4(6):324
A report on the Genomics, Proteomics and Bioinformatics Thematic Meeting during the 2003 American Society for Biochemistry and Molecular Biology (ASBMB) Annual Meeting, San Diego, USA, 11-15 April 2003. 相似文献
92.
Background
The power of microarray analysis can be realized only if data is systematically archived and linked to biological annotations as well as analysis algorithms. 相似文献93.
Protein tyrosine phosphorylation plays a regulatory role in a multitude of physiological processes in sperm. Changes in protein tyrosine phosphorylation, viability, and motility were studied as a function of extended incubation of bovine sperm in vitro at ambient temperature (18-20 degrees C). Fresh ejaculates were incubated after dilution for 8 days. On Days 0, 2, 5, and 8, an aliquot of sperm was incubated with or without theophylline at 37 degrees C for 30 min prior to assessing sperm viability, motility, and tyrosine phosphorylation of soluble and whole-cell proteins. There was a time-dependent decline in sperm motility, which was to some extent reversed by incubation with theophylline. The sum of the phosphotyrosine signal from two soluble proteins (M(r) 67 000 and 36 000) declined with incubation time in both theophylline-treated and untreated sperm. There were major differences in the pattern of tyrosine phosphorylation during incubation between ejaculates from different bulls. Tyrosine phosphorylation of a number of proteins from whole-cell extracts increased in a time-dependent manner during in vitro incubation and was unaffected by the presence of theophylline in the medium. The oxygenation state of the incubation medium had profound effects on sperm motility, viability, and tyrosine phosphorylation of proteins from whole-cell extracts. Sperm motility and viability declined more rapidly under aerobic compared with anaerobic conditions. Tyrosine phosphorylation of proteins from whole-cell extracts increased considerably during anaerobic incubation, while there was no significant change during aerobic incubation. This increase in phosphorylation due to anaerobic incubation was reversed when sperm were transferred from an anaerobic to an aerobic environment, indicating that the oxygenation state of the medium regulates both protein tyrosine kinases and phosphatases. In addition, sperm incubated under aerobic conditions for 5 days retained the ability to phosphorylate proteins when transferred to an anaerobic environment. The increase in protein tyrosine phosphorylation during in vitro incubation took place in a medium that did not contain capacitating substances such as heparin, sodium bicarbonate, or BSA. It transpired over a time scale of days and was not augmented by an increase in intracellular cAMP concentration through phosphodiesterase inhibition. Protein tyrosine phosphorylation during extended in vitro incubation at ambient temperature was significantly inhibited by the presence of oxygen in the medium. 相似文献
94.
Faraldo-Gómez JD Kutluay E Jogini V Zhao Y Heginbotham L Roux B 《Journal of molecular biology》2007,365(3):649-662
The mechanism of intracellular blockade of the KcsA potassium channel by tetrabutylammonium (TBA) is investigated through functional, structural and computational studies. Using planar-membrane electrophysiological recordings, we characterize the binding kinetics as well as the dependence on the transmembrane voltage and the concentration of the blocker. It is found that the apparent affinity of the complex is significantly greater than that of any of the eukaryotic K(+) channels studied previously, and that the off-rate increases with the applied transmembrane voltage. In addition, we report a crystal structure of the KcsA-TBA complex at 2.9 A resolution, with TBA bound inside the large hydrophobic cavity located at the center of the channel, consistent with the results of previous functional and structural studies. Of particular interest is the observation that the presence of TBA has a negligible effect on the channel structure and on the position of the potassium ions occupying the selectivity filter. Inspection of the electron density corresponding to TBA suggests that the ligand may adopt more than one conformation in the complex, though the moderate resolution of the data precludes a definitive interpretation on the basis of the crystallographic refinement methods alone. To provide a rationale for these observations, we carry out an extensive conformational sampling of an atomic model of TBA bound in the central cavity of KcsA, using the Hamiltonian replica-exchange molecular dynamics simulation method. Comparison of the simulated and experimental density maps indicates that the latter does reflect at least two distinct binding orientations of TBA. The simulations show also that the relative population of these binding modes is dependent on the ion configuration occupying the selectivity filter, thus providing a clue to the nature of the voltage-dependence of the binding kinetics. 相似文献
95.
Suberin: biosynthesis,regulation, and polymer assembly of a protective extracellular barrier 总被引:2,自引:0,他引:2
Sollapura J. Vishwanath Camille Delude Frédéric Domergue Owen Rowland 《Plant cell reports》2015,34(4):573-586
Suberin is a lipid-phenolic biopolyester deposited in the cell walls of certain boundary tissue layers of plants, such as root endodermis, root and tuber peridermis, and seed coats. Suberin serves as a protective barrier in these tissue layers, controlling, for example, water and ion transport. It is also a stress-induced anti-microbial barrier. The suberin polymer contains a variety of C16–C24 chain-length aliphatics, such as ω-hydroxy fatty acids, α,ω-dicarboxylic fatty acids, and primary fatty alcohols. Suberin also contains high amounts of glycerol and phenolics, especially ferulic acid. In addition, non-covalently linked waxes are likely associated with the suberin polymer. This review focusses on the suberin biosynthetic enzymes identified to date, which include β-ketoacyl-CoA synthases, fatty acyl reductases, long-chain acyl-CoA synthetases, cytochrome P450 monooxygenases, glycerol 3-phosphate acyltransferases, and phenolic acyltransferases. We also discuss recent advances in our understanding of the transport of suberin components intracellularly and to the cell wall, polymer assembly, and the regulation of suberin deposition. 相似文献
96.
Karpuj MV Giles K Gelibter-Niv S Scott MR Lingappa VR Szoka FC Peretz D Denetclaw W Prusiner SB 《Molecular medicine (Cambridge, Mass.)》2007,13(3-4):190-198
Prions are composed solely of the disease-causing prion protein (PrPSc) that is formed from the cellular isoform PrPC by a posttranslational process. Here we report that short phosphorothioate DNA (PS-DNA) oligonucleotides diminished the levels of both PrPC and PrPSc in prion-infected neuroblastoma (ScN2a) cells. The effect of PS-DNA on PrP levels was independent of the nucleotide sequence. The effective concentration (EC50) of PS-DNA required to achieve half-maximal diminution of PrPSc was approximately 70 nM, whereas the EC50 of PS-DNA for PrPC was more than 50-fold greater. This finding indicated that diminished levels of PrPSc after exposure to PS-DNA are unlikely to be due to decreased PrPC levels. Bioassays in transgenic mice demonstrated a substantial diminution in the prion infectivity after ScN2a cells were exposed to PS-DNAs. Whether PS-DNA will be useful in the treatment of prion disease in people or livestock remains to be established. 相似文献
97.
Ankanahalli N. Nanjaraj Urs Chandrasekaran Ramakrishnan Vikram Joshi Kanve Nagaraj Suvilesh Teregowda Veerabasappa Gowda Devadasan Velmurugan Bannikuppe Sannanaik Vishwanath 《PloS one》2015,10(8)
Viperbite is often associated with severe local toxicity, including progressive hemorrhage and myotoxicity, persistent even after the administration of anti-snake venom (ASV). In the recent past, investigations have revealed the orchestrated actions of Zn2+ metalloproteases (Zn2+MPs), phospholipase A2s (PLA2s) and hyaluronidases (HYs) in the onset and progression of local toxicity from the bitten site. As a consequence, venom researchers and medical practitioners are in deliberate quest of potent molecules alongside ASV to tackle the brutal local manifestations induced by aforesaid venom toxins. Based on these facts, we have demonstrated the protective efficacy of inhibitor cocktail containing equal ratios of N,N,N’,N’-tetrakis (2-pyridylmethyl) ethane-1,2-diamine (TPEN) and silymarin (SLN) against progressive local toxicity induced by Echis carinatus venom (ECV). In our previous study we have shown the inhibitory potentials of TPEN towards Zn2+MPs of ECV (IC50: 6.7 μM). In this study we have evaluated in vitro inhibitory potentials of SLN towards PLA2s (IC50: 12.5 μM) and HYs (IC50: 8 μM) of ECV in addition to docking studies. Further, we have demonstrated the protection of ECV induced local toxicity with 10 mM inhibitor cocktail following 15, 30 min (for hemorrhage and myotoxicity); 60 min (for hemorrhage alone) of ECV injection in murine model. The histological examination of skin and thigh muscle sections taken out from the site of ECV injection substantiated the overall protection offered by inhibitor cocktail. In conclusion, the protective efficacy of inhibitor cocktail is of high interest and can be administered locally alongside ASV to treat severe local toxicity. 相似文献
98.
Rutkowski DT Ott CM Polansky JR Lingappa VR 《The Journal of biological chemistry》2003,278(32):30365-30372
An interaction between an N-terminal signal sequence and the translocon leads to the initiation of protein translocation into the endoplasmic reticulum lumen. Subsequently, folding and modification of the substrate rapidly ensue. The close temporal coordination of these processes suggests that they may be structurally and functionally coordinated as well. Here we show that information encoded in the hydrophobic domain of a signal sequence influences the timing and efficiency of at least two steps in maturation, namely N-linked glycosylation and signal sequence cleavage. We demonstrate that these consequences correlate with and likely stem from the nature of the initial association made between the signal sequence and the translocon during the initiation of translocation. We propose a model by which these maturational events are controlled by the signal sequence-translocon interaction. Our work demonstrates that the pathway taken by a nascent chain through post-translational maturation depends on information encoded in its signal sequence. 相似文献
99.
Physoschistura chindwinensis, a new balitorid species, is described from the Chindwin basin, Manipur, India. It is easily distinguished from congeners by the combination of characters: a dorsal fin with three simple and 8? branched rays; body with 13–17 dark-brown bars on the sides, and 11–16 dark-brown saddles; interorbital space with a rectangular dark-brown shield-like mark; a caudal fin with 8?+?8 branched rays; a moderately developed axillary pelvic lobe; males with a suborbital flap; preoperculomandibular canal with seven pores; and an air bladder with a well-formed free posterior chamber. 相似文献
100.
N. Al-Somai P. C. Molan Dr. R. Vishwanath P. Shannon 《Molecular reproduction and development》1994,39(3):328-336
Bovine seminal plasma proteins are in an aggregated form of high molecular weight in their native state. By immobilisation on a cation exchanger with exposure to disaggregating conditions (i.e., acetonitrile and low pH), the high-molecular-weight aggregates could be dissociated to slowly release the low-molecular-weight components. The anionic component released from the cation exchanger during disaggregation was collected by adsorption on a hydrophobic interaction column. The cationic component remaining on the cation exchanger was eluted with NaOH. Both components were found on gel permeation chromatography to be <5 kDa. SDS—PAGE of the various fractions showed that component of low molecular weight were still in an aggregated form. These components resulting from the disaggregation process have detrimental effects on sperm motility and the effects were more substantial compared with that of whole seminal plasma. All the cationic components were significantly detrimental to sperm motility, especially the fractions of low molecular weight. The anionic fractions reduced sperm motility when in an aggregated state. The isolated anionic peptide was not detrimental in its free form. In all fractions the peptides tended to re-aggregate to a higher molecular weight under neutral conditions, however, the isolated anionic peptide (molecular weight <1,500) failed to do so. © Wiley-Liss, Inc. 相似文献