全文获取类型
收费全文 | 374篇 |
免费 | 17篇 |
出版年
2022年 | 1篇 |
2020年 | 1篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 6篇 |
2016年 | 9篇 |
2015年 | 16篇 |
2014年 | 9篇 |
2013年 | 20篇 |
2012年 | 28篇 |
2011年 | 27篇 |
2010年 | 17篇 |
2009年 | 12篇 |
2008年 | 25篇 |
2007年 | 27篇 |
2006年 | 32篇 |
2005年 | 28篇 |
2004年 | 35篇 |
2003年 | 22篇 |
2002年 | 13篇 |
2001年 | 7篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1996年 | 4篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 6篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有391条查询结果,搜索用时 62 毫秒
91.
Vitamin A (all-trans retinol) and all-trans retinoid acid (ATRA) interacted with human annexin A6 (AnxA6) as evidenced by AnxA6-induced blue shift of retinoid absorption maxima, by AnxA6-Trp fluorescence quenching and by a fluorescence resonance energy transfer from a Trp residue of AnxA6 to retinol. In addition, both retinoids stimulated the calcium-dependent binding of AnxA6 to liposomes, accompanied by oligomerization of AnxA6. Up to our knowledge, it is a first report supporting the hypothesis of a direct implication of AnxA6 in vitamin A-dependent tissue mineralization. 相似文献
92.
Spiechowicz M Bernstein HG Dobrowolny H Leśniak W Mawrin C Bogerts B Kuźnicki J Filipek A 《Neurochemistry international》2006,49(5):487-493
Sgt1 was discovered as a protein required for the mitotic activity of kinetochore and for the activity of ubiquitin ligase in yeast [Kitagawa, K., Skowyra, D., Elledge, S.J., Harper, J.W., Hieter, P., 1999. SGT1 encodes an essential component of the yeast kinetochore assembly pathway and a novel subunit of the SCF ubiquitin ligase complex. Mol. Cell 4, 21-33.]. Later, Sgt1 was identified in different organisms including mammals where it was found at high level in the brain. To understand Sgt1 function in this tissue we analyzed its localization in human brain by immunohistochemistry. In normal brain we observed Sgt1-immunostaining in Purkinje cells of the cerebellum, in granule cells of the dentate gyrus of the hippocampus and in multiple neurons of the cortex. By Western blotting we found a higher level of this protein in the cortex than in the cerebellum. Subsequent morphometric analyses showed that the density of Sgt1-immunopositive neurons varied in different cortical regions. The highest density of Sgt1-immunopositive cells was seen in the temporal cortex (from 1.2% to 5.7%), and the lowest - in the entorhinal cortex (from 0 to 1.1% of all neurons). We next compared the density of Sgt1-immunopositive neurons in cortical layers of healthy aged and Alzheimer's disease (AD) brain sections. A significant decrease in Sgt1-immunopositive neurons was found in the temporal (up to 25-fold), angular (up to 11-fold) and posterior cingulate cortex (up to five-fold). In the entorhinal and precentral cortex the reduction of Sgt1-immunopositive neurons was only about two-fold in AD brains as compared to healthy aged ones. The presence of Sgt1 in post-mitotic neurons indicates the involvement of this protein in a process different from that required for activity of the kinetochore. Decreased immunostaining in AD cortex point to Sgt1 as a possible marker of neurons degenerating in AD. 相似文献
93.
Mechanical unfolding of single bacteriorhodopsins from a membrane bilayer is studied using molecular dynamics simulations. The initial conformation of the lipid membrane is determined through all-atom simulations and then its coarse-grained representation is used in the studies of stretching. A Go-like model with a realistic contact map and with Lennard-Jones contact interactions is applied to model the protein-membrane system. The model qualitatively reproduces the experimentally observed differences between force-extension patterns obtained on bacteriorhodopsin at different temperatures and predicts a lack of symmetry in the choice of the terminus to pull by. It also illustrates the decisive role of the interactions of the protein with the membrane in determining the force pattern and thus the stability of transmembrane proteins. 相似文献
94.
Xu Q Schwarzenbacher R Krishna SS McMullan D Agarwalla S Quijano K Abdubek P Ambing E Axelrod H Biorac T Canaves JM Chiu HJ Elsliger MA Grittini C Grzechnik SK DiDonato M Hale J Hampton E Han GW Haugen J Hornsby M Jaroszewski L Klock HE Knuth MW Koesema E Kreusch A Kuhn P Miller MD Moy K Nigoghossian E Paulsen J Reyes R Rife C Spraggon G Stevens RC van den Bedem H Velasquez J White A Wolf G Hodgson KO Wooley J Deacon AM Godzik A Lesley SA Wilson IA 《Proteins》2006,64(3):808-813
95.
Jin KK Krishna SS Schwarzenbacher R McMullan D Abdubek P Agarwalla S Ambing E Axelrod H Canaves JM Chiu HJ Deacon AM DiDonato M Elsliger MA Feuerhelm J Godzik A Grittini C Grzechnik SK Hale J Hampton E Haugen J Hornsby M Jaroszewski L Klock HE Knuth MW Koesema E Kreusch A Kuhn P Lesley SA Miller MD Moy K Nigoghossian E Okach L Oommachen S Paulsen J Quijano K Reyes R Rife C Stevens RC Spraggon G van den Bedem H Velasquez J White A Wolf G Han GW Xu Q Hodgson KO Wooley J Wilson IA 《Proteins》2006,63(4):1112-1118
96.
Cyril Thouverey Agnieszka Strzelecka‐Kiliszek Marcin Balcerzak René Buchet Slawomir Pikula 《Journal of cellular biochemistry》2009,106(1):127-138
In bone, mineralization is tightly regulated by osteoblasts and hypertrophic chondrocytes which release matrix vesicles (MVs) and control extracellular ionic conditions and matrix composition. MVs are the initial sites of hydroxyapatite (HA) mineral formation. Despite growing knowledge about their morphology and function, their biogenesis is not well understood. The purpose of this work was to determine the source of MVs in osteoblast lineage, Saos‐2 cells, and to check whether MVs originated from microvilli. Microvilli were isolated from the apical plasma membrane of Saos‐2 cells. Their morphology, structure, and function were compared with those of MVs. The role of actin network in MV release was investigated by using microfilament perturbing drugs. When examined by electron microscopy MVs and microvillar vesicles were found to exhibit similar morphology with trilaminar membranes and diameters in the same range. Both types of vesicles were able to induce HA formation. Their electrophoretic profiles displayed analogous enrichment in alkaline phosphatase, Na+/K+ ATPase, and annexins A2 and A6. MVs and microvillar vesicles exhibited almost the same lipid composition with a higher content of cholesterol, sphingomyelin, and phosphatidylserine as compared to plasma membrane. Finally, cytochalasin D, which inhibits actin polymerization, was found to stimulate release of MVs. Our findings were consistent with the hypothesis that MVs originated from cell microvilli and that actin filament disassembly was involved in their biogenesis. J. Cell. Biochem. 106: 127–138, 2009. © 2008 Wiley‐Liss, Inc. 相似文献
97.
Izabela Fokt Slawomir Szymanski Stanislaw Skora Marcin Cybulski Timothy Madden Waldemar Priebe 《Carbohydrate research》2009,344(12):340
Modified d-glucose and d-mannose analogs are potentially clinically useful metabolic inhibitors. Biological evaluation of 2-deoxy-2-halo analogs has been impaired by limited availability and lack of efficient methods for their preparation. We have developed practical synthetic approaches to 2-deoxy-2-fluoro-, 2-chloro-2-deoxy-, 2-bromo-2-deoxy-, and 2-deoxy-2-iodo derivatives of d-glucose and d-mannose that exploit electrophilic addition reactions to a commercially available 3,4,6-tri-O-acetyl-d-glucal. 相似文献
98.
Among the structurally similar guanidinonaltrindole (GNTI) compounds, 5′-GNTI is an antagonist while 6′-GNTI is an agonist
of the κOR opioid receptor. To explore how a subtle alteration of the ligand structure influences the receptor activity, we
investigated two concurrent processes: the final steps of ligand binding at the receptor binding site and the initial steps
of receptor activation. To trace these early activation steps, the membranous part of the receptor was built on an inactive
receptor template while the extracellular loops were built using the ab initio CABS method. We used the simulated annealing
procedure for ligand docking and all-atom molecular dynamics simulations to determine the immediate changes in the structure
of the ligand–receptor complex. The binding of an agonist, in contrast to an antagonist, induced the breakage of the “3–7
lock” between helices TM3 and TM7. We also observed an action of the extended rotamer toggle switch which suggests that those
two switches are interdependent. 相似文献
99.
It is becoming increasingly apparent that G protein-coupled receptors (GPCRs) can exist and function as oligomers. This notion
differs from the classical view of signaling wherein the receptor has been presumed to be monomeric. Despite this shift in
views, the interpretation of data related to GPCR function is still largely carried out within the framework of a monomeric
receptor. Rhodopsin is a prototypical GPCR that initiates phototransduction. Like other GPCRs, the activity of rhodopsin is
regulated by phosphorylation and the binding of arrestin. In the current investigation, we have explored by modeling methods
the interaction of rhodopsin and arrestin under the assumption that either one or two rhodopsin molecules bind each arrestin
molecule. The dimeric receptor framework may provide a more accurate representation of the system and is therefore likely
to lead to a better and more accurate understanding of GPCR signaling. 相似文献
100.
G protein-coupled receptor (GPCR)-mediated signal transduction has been studied for more than a century. Despite the intense focus on this class of proteins, a molecular understanding of what constitutes the functional form of the receptor is still uncertain. GPCRs have traditionally been conceptualized as monomeric proteins, and this view has changed little over the years until relatively recently. Recent biochemical and biophysical studies have challenged this traditional concept, and point instead to a mechanistic view of signal transduction wherein the receptor functions as an oligomer. Cooperative interactions within such an oligomeric array may be critical for the propagation of an external signal across the cell membrane and to the G protein, and may therefore underlie the mechanistic basis of signaling. 相似文献