全文获取类型
收费全文 | 100篇 |
免费 | 3篇 |
出版年
2020年 | 1篇 |
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 2篇 |
2015年 | 6篇 |
2014年 | 3篇 |
2012年 | 3篇 |
2011年 | 6篇 |
2010年 | 4篇 |
2009年 | 4篇 |
2008年 | 3篇 |
2007年 | 3篇 |
2006年 | 1篇 |
2005年 | 1篇 |
2004年 | 3篇 |
2003年 | 2篇 |
2001年 | 8篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 4篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1930年 | 1篇 |
排序方式: 共有103条查询结果,搜索用时 187 毫秒
1.
Postsynaptic responses evoked by stimulation of the descending tract and dorsal roots were investigated by means of intracellular microelectrodes in experiments on preparation of the isolated lamprey spinal cord. Besides giant reticulospinal (Mullerian) axons, a broad spectrum of descending fibers and dorsal-root afferents were shown to form synaptic inputs with both chemical and electrical mechanisms of transmission with motoneurons, as revealed by the sensitivity of the corresponding PSPs to absence of calcium ions and excess of magnesium ions in the external medium. During combined stimulation electrotonic PSPs may have a rapid temporal course characteristic of elementary responses, but they may also lead to smooth and slow depolarization of the postsynaptic membrane, evidence that they may perform not only a mediator but also an integrative function.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 9, No. 5, pp. 512–517, September–October, 1977. 相似文献
2.
Tong Y Brandt GS Li M Shapovalov G Slimko E Karschin A Dougherty DA Lester HA 《The Journal of general physiology》2001,117(2):103-118
Tyrosine side chains participate in several distinct signaling pathways, including phosphorylation and membrane trafficking. A nonsense suppression procedure was used to incorporate a caged tyrosine residue in place of the natural tyrosine at position 242 of the inward rectifier channel Kir2.1 expressed in Xenopus oocytes. When tyrosine kinases were active, flash decaging led both to decreased K(+) currents and also to substantial (15-26%) decreases in capacitance, implying net membrane endocytosis. A dominant negative dynamin mutant completely blocked the decaging-induced endocytosis and partially blocked the decaging-induced K(+) channel inhibition. Thus, decaging of a single tyrosine residue in a single species of membrane protein leads to massive clathrin-mediated endocytosis; in fact, membrane area equivalent to many clathrin-coated vesicles is withdrawn from the oocyte surface for each Kir2.1 channel inhibited. Oocyte membrane proteins were also labeled with the thiol-reactive fluorophore tetramethylrhodamine-5-maleimide, and manipulations that decreased capacitance also decreased surface membrane fluorescence, confirming the net endocytosis. In single-channel studies, tyrosine kinase activation decreased the membrane density of active Kir2.1 channels per patch but did not change channel conductance or open probability, in agreement with the hypothesis that tyrosine phosphorylation results in endocytosis of Kir2.1 channels. Despite the Kir2.1 inhibition and endocytosis stimulated by tyrosine kinase activation, neither Western blotting nor (32)P labeling produced evidence for direct tyrosine phosphorylation of Kir2.1. Therefore, it is likely that tyrosine phosphorylation affects Kir2.1 function indirectly, via interactions between clathrin adaptor proteins and a tyrosine-based sorting motif on Kir2.1 that is revealed by decaging the tyrosine side chain. These interactions inhibit a fraction of the Kir2.1 channels, possibly via direct occlusion of the conduction pathway, and also lead to endocytosis, which further decreases Kir2.1 currents. These data establish that side chain decaging can provide valuable time-resolved data about intracellular signaling systems. 相似文献
3.
Becker CF Clayton D Shapovalov G Lester HA Kochendoerfer GG 《Bioconjugate chemistry》2004,15(5):1118-1124
A synthesis strategy for the on-resin assembly of luminescent lanthanide chelates from commercially available compounds was developed. Advantages of the approach include the absence of spacers between the metal ion and the attachment site, and the compatibility with typical chemical protein synthesis protection schemes. Methoxycoumarin-labeled lysine and tris(tert-butyl)-DOTA were consecutively coupled with high efficiency to a free amino group in otherwise fully protected peptide segments using standard peptide synthesis methods. Addition of stoichiometric amounts of Tb(3+) to the modified, cleaved, and purified peptides yielded the desired lanthanide chelate. Incorporation of this label into a chemically synthesized, full-length mechanosensitive channel of large conductance (MscL) of E. coli and subsequent reconstitution into vesicles resulted in a functional mechanosensitive channel of comparable conductance to the wild-type channel. However, this channel required increased suction to gate. Excitation of the antenna molecule methoxycoumarin at 336 nm resulted in an emission spectrum typical for Tb(3+) and a luminescence lifetime of 0.67 ms. The location of the probe close to the backbone of this protein may provide precise information about conformational changes during channel opening from LRET studies. 相似文献
4.
Shnol' SE Rubinshteĭn IA Zenchenko KI Zenchenko TA Udal'tsova NV Kondradov AA Shapovalov SN Makarevich AV Gorshkov ES Troshichev OA 《Biofizika》2003,48(6):1123-1131
The detailed structure of histograms constructed from the results of synchronous measurements of the alpha-activity of 239Pu microsamples, conducted in Pushchino (Moscow Region, Russia) and on board the ship "Academician Fedorov" during the Arctic and Antarctic expeditions (2000 and 2001) was analyzed. It was shown that, if the histograms were constructed over a total period of 15 min and more, the "local zone effect" and the circadian periodicity in the similarity of histogram structure, observed during measurements in Pushchino, are not found in measurements on board the ship near the North Pole (latitude 82 degrees). If the histograms were constructed over a total time of 1 min, a strict periodicity ("stellar day" 23 h 56 min) in the appearance of similar histograms in Pushchino and the Arctic and a strict synchronicity of the appearance of similar histograms of measurements in Pushchino and on board the ship at the same local geographical time were observed. During the Antarctic expedition, the effect of synchronicity of the appearance of similar histograms in Pushchino and on board the ship decreased as the ship moved towards the South Pole and the difference in latitude between the points of measurements increased. 相似文献
5.
Anton Golovnin Larisa Melnikova Igor Shapovalov Margarita Kostyuchenko Pavel Georgiev 《PloS one》2015,10(10)
Recent data suggest that insulators organize chromatin architecture in the nucleus. The best studied Drosophila insulator proteins, dCTCF (a homolog of the vertebrate insulator protein CTCF) and Su(Hw), are DNA-binding zinc finger proteins. Different isoforms of the BTB-containing protein Mod(mdg4) interact with Su(Hw) and dCTCF. The CP190 protein is a cofactor for the dCTCF and Su(Hw) insulators. CP190 is required for the functional activity of insulator proteins and is involved in the aggregation of the insulator proteins into specific structures named nuclear speckles. Here, we have shown that the nuclear distribution of CP190 is dependent on the level of EAST protein, an essential component of the interchromatin compartment. EAST interacts with CP190 and Mod(mdg4)-67.2 proteins in vitro and in vivo. Over-expression of EAST in S2 cells leads to an extrusion of the CP190 from the insulator bodies containing Su(Hw), Mod(mdg4)-67.2, and dCTCF. In consistent with the role of the insulator bodies in assembly of protein complexes, EAST over-expression led to a striking decrease of the CP190 binding with the dCTCF and Su(Hw) dependent insulators and promoters. These results suggest that EAST is involved in the regulation of CP190 nuclear localization. 相似文献
6.
Protein side chains make most of the specific contacts between proteins and other molecules, and their conformational properties have been studied for many years. These properties have been analyzed primarily in the form of rotamer libraries, which cluster the observed conformations into groups and provide frequencies and average dihedral angles for these groups. In recent years, these libraries have improved with higher resolution structures and using various criteria such as high thermal factors to eliminate side chains that may be misplaced within the crystallographic model coordinates. Many of these side chains have highly non-rotameric dihedral angles. The origin of side chains with high B-factors and/or with non-rotameric dihedral angles is of interest in the determination of protein structures and in assessing the prediction of side chain conformations. In this paper, using a statistical analysis of the electron density of a large set of proteins, it is shown that: (1) most non-rotameric side chains have low electron density compared to rotameric side chains; (2) up to 15% of chi1 non-rotameric side chains in PDB models can clearly be fit to density at a single rotameric conformation and in some cases multiple rotameric conformations; (3) a further 47% of non-rotameric side chains have highly dispersed electron density, indicating potentially interconverting rotameric conformations; (4) the entropy of these side chains is close to that of side chains annotated as having more than one chi(1) rotamer in the crystallographic model; (5) many rotameric side chains with high entropy clearly show multiple conformations that are not annotated in the crystallographic model. These results indicate that modeling of side chains alternating between rotamers in the electron density is important and needs further improvement, both in structure determination and in structure prediction. 相似文献
7.
Dimitra Gkika Loic Lemonnier George Shapovalov Dmitri Gordienko Céline Poux Michela Bernardini Alexandre Bokhobza Gabriel Bidaux Cindy Degerny Kathye Verreman Basma Guarmit Mohamed Benahmed Yvan de Launoit Rene J.M. Bindels Alessandra Fiorio Pla Natalia Prevarskaya 《The Journal of cell biology》2015,208(1):89-107
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. 相似文献
8.
Polyana C Tizioto Jeremy F Taylor Jared E Decker Caio F Gromboni Mauricio A Mudadu Robert D Schnabel Luiz L Coutinho Gerson B Mour?o Priscila SN Oliveira Marcela M Souza James M Reecy Renata T Nassu Flavia A Bressani Patricia Tholon Tad S Sonstegard Mauricio M Alencar Rymer R Tullio Ana RA Nogueira Luciana CA Regitano 《遗传、选种与进化》2015,47(1)
9.
10.
Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell death
下载免费PDF全文
![点击此处可从《The Journal of general physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hirn C Shapovalov G Petermann O Roulet E Ruegg UT 《The Journal of general physiology》2008,132(2):199-208
Duchenne muscular dystrophy (DMD) is a hereditary degenerative disease manifested by the absence of dystrophin, a structural, cytoskeletal protein, leading to muscle degeneration and early death through respiratory and cardiac muscle failure. Whereas the rise of cytosolic Ca(2+) concentrations in muscles of mdx mouse, an animal model of DMD, has been extensively documented, little is known about the mechanisms causing alterations in Na(+) concentrations. Here we show that the skeletal muscle isoform of the voltage-gated sodium channel, Na(v)1.4, which represents over 90% of voltage-gated sodium channels in muscle, plays an important role in development of abnormally high Na(+) concentrations found in muscle from mdx mice. The absence of dystrophin modifies the expression level and gating properties of Na(v)1.4, leading to an increased Na(+) concentration under the sarcolemma. Moreover, the distribution of Na(v)1.4 is altered in mdx muscle while maintaining the colocalization with one of the dystrophin-associated proteins, syntrophin alpha-1, thus suggesting that syntrophin is an important linker between dystrophin and Na(v)1.4. Additionally, we show that these modifications of Na(v)1.4 gating properties and increased Na(+) concentrations are strongly correlated with increased cell death in mdx fibers and that both cell death and Na(+) overload can be reversed by 3 nM tetrodotoxin, a specific Na(v)1.4 blocker. 相似文献