全文获取类型
收费全文 | 484篇 |
免费 | 41篇 |
专业分类
525篇 |
出版年
2023年 | 2篇 |
2022年 | 4篇 |
2021年 | 15篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 8篇 |
2017年 | 5篇 |
2016年 | 13篇 |
2015年 | 12篇 |
2014年 | 22篇 |
2013年 | 32篇 |
2012年 | 34篇 |
2011年 | 46篇 |
2010年 | 20篇 |
2009年 | 24篇 |
2008年 | 28篇 |
2007年 | 26篇 |
2006年 | 34篇 |
2005年 | 20篇 |
2004年 | 21篇 |
2003年 | 17篇 |
2002年 | 21篇 |
2001年 | 2篇 |
2000年 | 5篇 |
1999年 | 4篇 |
1998年 | 10篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 8篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 8篇 |
1977年 | 6篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1967年 | 2篇 |
1950年 | 1篇 |
排序方式: 共有525条查询结果,搜索用时 15 毫秒
41.
Citri A Harari D Shohat G Ramakrishnan P Gan J Lavi S Eisenstein M Kimchi A Wallach D Pietrokovski S Yarden Y 《The Journal of biological chemistry》2006,281(20):14361-14369
Hsp90 is a highly abundant chaperone whose clientele includes hundreds of cellular proteins, many of which are central players in key signal transduction pathways and the majority of which are protein kinases. In light of the variety of Hsp90 clientele, the mechanism of selectivity of the chaperone toward its client proteins is a major open question. Focusing on human kinases, we have demonstrated that the chaperone recognizes a common surface in the amino-terminal lobe of kinases from diverse families, including two newly identified clients, NFkappaB-inducing kinase and death-associated protein kinase, and the oncoprotein HER2/ErbB-2. Surface electrostatics determine the interaction with the Hsp90 chaperone complex such that introduction of a negative charge within this region disrupts recognition. Compiling information on the Hsp90 dependence of 105 protein kinases, including 16 kinases whose relationship to Hsp90 is first examined in this study, reveals that surface features, rather than a contiguous amino acid sequence, define the capacity of the Hsp90 chaperone machine to recognize client kinases. Analyzing Hsp90 regulation of two major signaling cascades, the mitogen-activated protein kinase and phosphatidylinositol 3-kinase, leads us to propose that the selectivity of the chaperone to specific kinases is functional, namely that Hsp90 controls kinases that function as hubs integrating multiple inputs. These lessons bear significance to pharmacological attempts to target the chaperone in human pathologies, such as cancer. 相似文献
42.
Either protective or toxic effects of cannabinoids on cell survival have been reported extensively in the literature; however,
the factors that determine the direction of the effect are still obscured. In this study we have used the neuroblastoma cell
line N18TG2 that expresses CB1 cannabinoid receptors to investigate several factors that may determine the consequences of
exposure to cannabinoid agonists. Cells that were grown under optimal, stressful, or differentiating conditions were exposed
to cannabinoid agonists and then assayed for cell viability by measuring MTT, LDH, and caspase-3 activity. Various cannabinoid
agonists (CP 55,940, ∆9-THC, HU-210, and WIN 55,212-2) failed to affect cell viability when the cells were grown under optimal
conditions. On the other hand, the same agonists significantly reduced cell viability when the cells were grown under stressful
conditions (glucose- and serum-free medium), while enhancing the viability of cells grown in differentiation medium (0.5%
serum and 1.5% DMSO). The toxic/protective profile was not dependent on the type or the concentration of the cannabinoid agonist
that was applied. The cannabinoid agonist CP 55,940 similarly affected the non-neuronal HEK-293 cells that were grown under
stressful conditions only when they expressed CB1 receptors. Our results shed light on the conflicting reports regarding the
protective or toxic effects of cannabinoids in vitro and indicate that cannabinoids may activate different intracellular signaling
mechanisms, depending on the state of the cell, thus leading to different physiological consequences. 相似文献
43.
Understanding the structural basis of protein-protein interactions (PPIs) may shed light on the organization and functioning of signal transduction and metabolic networks and may assist in structure-based design of ligands (drugs) targeting protein-protein interfaces. The residues at the bimolecular interface, designated as the hot spots, contribute most of the free binding energy of PPI. To date, there is no conclusive atomistic explanation for the unique functional properties of the hot spots. We hypothesized that backbone compliance may play a role in protein-protein recognition and in the mechanism of binding of small-molecule compounds to protein surfaces. We used a steered molecular dynamics simulation to explore the compliance properties of the backbone of surface-exposed residues in several model proteins: interleukin-2, mouse double minute protein 2 and proliferating cell nuclear antigen. We demonstrated that protein surfaces exhibit distinct patterns in which highly immobile residues form defined clusters ("stability patches") alternating with areas of moderate to high mobility. These "stability patches" tend to localize in functionally important regions involved in protein-protein recognition. We propose a mechanism by which the distinct structural organization of the hot spots may contribute to their role in mediating PPI and facilitating binding of structurally diverse small-molecule compounds to protein surfaces. 相似文献
44.
Are Biological Effects of Desert Shrubs More Important than Physical Effects on Soil Microorganisms?
Vegetation cover plays a major role in providing organic matter and in acting as a physical barrier, with both together contributing
to the formation of “fertile islands,” which play an active role in prolonging biological activity in desert ecosystems. By
undertaking this study, a long-term research, we designed an experiment to separate the two components—the physical and biotic
parts of the perennial plants—and to identify the factor that contributes the most to the ecosystem. The study site was located
in the northern Negev Desert, Israel, where 50 Hammada scoparia shrubs and 50 artificial plants were randomly marked. Soil samples were collected monthly over 3 years of research at three
locations: under the canopy of H. scoparia shrubs, in the vicinity of the artificial plants, and between the shrubs (control). The contribution to microbial activity
was measured by evaluation of the microbial community functions in soil. The functional aspects of the microbial community
that were measured were CO2 evolution, microbial biomass, microbial functional diversity, and the physiological profile of the community. The results
of this study are presented in two ways: (1) according to the three locations/treatments; and (2) according to the phenological
situation of the vegetation (annual and perennial plants) in the research field: the growing phase, the drying process, and
the absence of annual plants. The only parameters that were found to affect microbial activity were the contribution of the
organic matter of perennial shrubs and the growth of vegetation (annual and perennial) during the growing seasons. The physical
component was found to have no effect on soil microbial functional diversity, which elucidates the important contribution
of the desert shrub in enhancing biological multiplicity and activity. 相似文献
45.
Carbon to chlorophyll a (C:Chl) ratios, assimilation numbers (A.N.) and turnover times of natural populations of individual species and taxonomic
groups were extracted from a long-term database of phytoplankton wet-weight biomass, chlorophyll a concentrations, and primary production in Lake Kinneret, Israel. From a database spanning more than a decade, we selected
data for samples dominated by a single species or taxonomic group. The overall average of C:Chl was highest for cyanophytes
and lowest for diatoms, while chlorophytes and dinoflagellates showed intermediate values. When converting chlorophyll a to algal cellular carbon this variability should be taken into account. The variability in C:Chl within each phylum and species
(when data were available) was high and the variability at any particular sampling date tended to be greater than the temporal
variability. The average chlorophyll a-normalized rate of photosynthetic activity of cyanophytes was higher and that of the dinoflagellates lower than that of other
phyla. Turnover time of phytoplankton, calculated using primary productivity data at the depth of maximal photosynthetic rate,
was longest in dinoflagellates and shortest in cyanophytes, with diatoms and chlorophytes showing intermediate values. The
more extreme C:Chl and turnover times of dinoflagellates and cyanobacteria in comparison with chlorophytes and diatoms should
be taken into consideration when employed in ecological modeling. 相似文献
46.
47.
Flowering in the short-day plant Lemna paucicostata 6746 canbe induced under continuous light by the addition of ferricyanie,ferrocyanide or KCN to M-sucrose medium. Each substance is nearly10 times more effective when the flasks are covered by glassbeakers than when cotton plugs are used. By contrast, when floweringis induced under continuous light by copper or by short-daytreatment, neither flowering nor growth are affected by whetherglass beakers or cotton plugs are used. Ferricyanide, ferrocyanideand KCN are also able to induce long-day flowering when theplants are grown on Msucrose medium in small beakers that areplaced in a covered storage dish that also contains a solutionof one of these compounds. Addition of a KOH trap to the storagedish completely blocks the flowering induced by these compounds.If [14C]ferrocyanide is added to the storage dish both the M-sucrosemedium and the plants contain significant amounts of radioactivity,the amount of radioactivity being proportional to the floweringresponse. These results indicate that ferricyanide, ferrocyanideand KCN break down to release HCN and that it is the HCN whichis responsible for inducing flowering in L. paucicostata 6746under continuous light.
1Present address: Department of Biology, Osaka Kyoiku University,Ikeda, Osaka 563, Japan.
2Present address: Institute of Horticulture, The Volcani Center,P. O. B. 6, Bet-Dagan, Israel. (Received January 17, 1983; Accepted March 24, 1983) 相似文献
48.
High‐density molecular characterization and association mapping in Ethiopian durum wheat landraces reveals high diversity and potential for wheat breeding 下载免费PDF全文
Dejene Kassahun Mengistu Yosef Gebrehawaryat Kidane Marcello Catellani Elisabetta Frascaroli Carlo Fadda Mario Enrico Pè Matteo Dell'Acqua 《Plant biotechnology journal》2016,14(9):1800-1812
Durum wheat (Triticum turgidum subsp. durum) is a key crop worldwide, and yet, its improvement and adaptation to emerging environmental threats is made difficult by the limited amount of allelic variation included in its elite pool. New allelic diversity may provide novel loci to international crop breeding through quantitative trait loci (QTL) mapping in unexplored material. Here, we report the extensive molecular and phenotypic characterization of hundreds of Ethiopian durum wheat landraces and several Ethiopian improved lines. We test 81 587 markers scoring 30 155 single nucleotide polymorphisms and use them to survey the diversity, structure, and genome‐specific variation in the panel. We show the uniqueness of Ethiopian germplasm using a siding collection of Mediterranean durum wheat accessions. We phenotype the Ethiopian panel for ten agronomic traits in two highly diversified Ethiopian environments for two consecutive years and use this information to conduct a genome‐wide association study. We identify several loci underpinning agronomic traits of interest, both confirming loci already reported and describing new promising genomic regions. These loci may be efficiently targeted with molecular markers already available to conduct marker‐assisted selection in Ethiopian and international wheat. We show that Ethiopian durum wheat represents an important and mostly unexplored source of durum wheat diversity. The panel analysed in this study allows the accumulation of QTL mapping experiments, providing the initial step for a quantitative, methodical exploitation of untapped diversity in producing a better wheat. 相似文献
49.
Yosef Geva Jonathan Crissman Eric C. Arakel Natalia Gómez‐Navarro Silvia G. Chuartzman Kyle R. Stahmer Blanche Schwappach Elizabeth A. Miller Maya Schuldiner 《Traffic (Copenhagen, Denmark)》2017,18(10):672-682
The endoplasmic reticulum (ER) is the entry site of proteins into the endomembrane system. Proteins exit the ER via coat protein II (COPII) vesicles in a selective manner, mediated either by direct interaction with the COPII coat or aided by cargo receptors. Despite the fundamental role of such receptors in protein sorting, only a few have been identified. To further define the machinery that packages secretory cargo and targets proteins from the ER to Golgi membranes, we used multiple systematic approaches, which revealed 2 uncharacterized proteins that mediate the trafficking and maturation of Pma1, the essential yeast plasma membrane proton ATPase. Ydl121c (Exp1) is an ER protein that binds Pma1, is packaged into COPII vesicles, and whose deletion causes ER retention of Pma1. Ykl077w (Psg1) physically interacts with Exp1 and can be found in the Golgi and coat protein I (COPI) vesicles but does not directly bind Pma1. Loss of Psg1 causes enhanced degradation of Pma1 in the vacuole. Our findings suggest that Exp1 is a Pma1 cargo receptor and that Psg1 aids Pma1 maturation in the Golgi or affects its retrieval. More generally our work shows the utility of high content screens in the identification of novel trafficking components. 相似文献
50.
Hiromi I. Wettersten Yosef Landesman Sharon Friedlander Sharon Shacham Michael Kauffman Robert H. Weiss 《PloS one》2014,9(12)