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Vikash Reebye Charlotte L. Bevan Mahrokh Nohadani Amin Hajitou Nagy A. Habib Paul J. Mintz 《Cellular signalling》2010,22(12):1874-1881
The underlying mechanism of failed androgen ablation therapy is unknown. It is recognised that under therapeutic conditions the androgen receptor (AR) remains functionally active independent of hormone stimulation and may function through an alternative pathway. We report a novel cooperative interaction between CRKL (an intracellular signalling adaptor protein) and the AR. We demonstrate by biochemical and genetic approaches that CRKL is associated with the AR complex and is localised in the nucleus of prostate cancer cells and patient tissue biopsies. The interaction between CRKL and the AR is functionally relevant as demonstrated by its presence on the enhancer region of an androgen regulated gene (human Kallikrein-2), its upregulation of PSA, and reduction in AR transactivation following its disruption by siRNA knockdown. In the presence of the AR inhibitor casodex, the expression of CRKL co-stimulated by growth factors is able to rescue AR activity independent of hormone. Our data provides insight on how a non-nuclear factor such as CRKL may interact with the AR complex to bypass hormone dependency by using an alternative growth factor signalling pathway in advanced prostate cancer. 相似文献
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We propose an overview of the mechanism of Ca2+ transport through the sarcoplasmic reticulum membrane via the Ca2+-ATPase. We describe cytoplasmic calcium binding, calcium occlusion in the membrane and lumenal calcium dissociation. A channel-like structure is discussed and related to structural data on the membranous domain of the Ca2+-ATPase.Abbreviations SR
Sarcoplasmic Reticulum
- AMPPNP
adenylyl-imidodiphosphate
- AMPPCP
adenylyl (,-methylene)-diphosphonate
- FITC
fluorescein 5-isothiocyanate
- NBD
4-nitrobenzo-2-oxa-1,3-diazole
- DCCD
dicyclohexylcarbodiimide 相似文献
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Wang Liang Tang Dalin Maehara Akiko Molony David Zheng Jie Samady Habib Wu Zheyang Lu Wenbin Zhu Jian Ma Genshan Giddens Don P. Stone Gregg W. Mintz Gary S. 《Biomechanics and modeling in mechanobiology》2019,18(5):1269-1280
Biomechanics and Modeling in Mechanobiology - Plaque progression and vulnerability are influenced by many risk factors. Our goal is to find a simple method to combine multiple risk factors for... 相似文献
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Protein-protein interfaces are regions between 2 polypeptide chains that are not covalently connected. Here, we have created a nonredundant interface data set generated from all 2-chain interfaces in the Protein Data Bank. This data set is unique, since it contains clusters of interfaces with similar shapes and spatial organization of chemical functional groups. The data set allows statistical investigation of similar interfaces, as well as the identification and analysis of the chemical forces that account for the protein-protein associations. Toward this goal, we have developed I2I-SiteEngine (Interface-to-Interface SiteEngine) [Data set available at http://bioinfo3d.cs.tau.ac.il/Interfaces; Web server: http://bioinfo3d.cs.tau.ac.il/I2I-SiteEngine]. The algorithm recognizes similarities between protein-protein binding surfaces. I2I-SiteEngine is independent of the sequence or the fold of the proteins that comprise the interfaces. In addition to geometry, the method takes into account both the backbone and the side-chain physicochemical properties of the interacting atom groups. Its high efficiency makes it suitable for large-scale database searches and classifications. Below, we briefly describe the I2I-SiteEngine method. We focus on the classification process and the obtained nonredundant protein-protein interface data set. In particular, we analyze the biological significance of the clusters and present examples which illustrate that given constellations of chemical groups in protein-protein binding sites may be preferred, and are observed in proteins with different structures and different functions. We expect that these would yield further information regarding the forces stabilizing protein-protein interactions. 相似文献
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Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
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A rapid method of sequentially phosphorylating picomole quantities of [3H]-araC to [3H]araCTP is described (ara = 1-β-d-arabinofuranosyl). The procedure utilizes a system of phosphorylating enzymes isolated from rat spleen and requires a single incubation step. The [3H]araCTP product is isolated by ion-exchange chromatography and analyzed by PEI-cellulose thin-layer chromatography. At low concentrations of [3H]araC as much as 80% can be phosphorylated to the triphosphate, and the produet may be obtained in radiochemical purity greater than 97%. 相似文献