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41.
Characterization of chicken TNFR superfamily decoy receptors,DcR3 and osteoprotegerin 总被引:5,自引:0,他引:5
Tumor necrosis factor (TNF) family ligands bind to death domain-containing TNF receptors (death receptors), which can subsequently activate intracellular signaling pathways to initiate caspase activity and apoptotic cell death. Decoy receptors, without intracellular death domains, have been reported to prevent cytotoxic effects by binding to and sequestering such ligands, or by interfering with death receptor trimerization. The chicken death receptors, Fas, TNFR1, DR6, and TVB, are constitutively expressed in a relatively wide variety of hen tissues. In this study, two chicken receptors with sequence homology to the mammalian decoys, DcR3 and osteoprotegerin, were identified and their pattern of expression was characterized. Unlike the previously identified chicken death receptors, the newly characterized decoy receptors show comparatively limited expression among tissues, suggesting a tissue-specific function. Finally, characterization of these chicken receptors further contributes to understanding the evolutionary divergence of TNFR superfamily members among vertebrate species. 相似文献
42.
A shape-based Gaussian docking function is constructed which uses Gaussian functions to represent the shapes of individual atoms. A set of 20 trypsin ligand-protein complexes are drawn from the Protein Data Bank (PDB), the ligands are separated from the proteins, and then are docked back into the active sites using numerical optimization of this function. It is found that by employing this docking function, quasi-Newton optimization is capable of moving ligands great distances [on average 7 A root mean square distance (RMSD)] to locate the correctly docked structure. It is also found that a ligand drawn from one PDB file can be docked into a trypsin structure drawn from any of the trypsin PDB files. This implies that this scoring function is not limited to more accurate x-ray structures, as is the case for many of the conventional docking methods, but could be extended to homology models. 相似文献
43.
Neuregulins: functions,forms, and signaling strategies 总被引:35,自引:0,他引:35
Falls DL 《Experimental cell research》2003,284(1):14-30
The neuregulins (NRGs) are cell-cell signaling proteins that are ligands for receptor tyrosine kinases of the ErbB family. The neuregulin family of genes has four members: NRG1, NRG2, NRG3, and NRG4. Relatively little is known about the biological functions of the NRG2, 3, and 4 proteins, and they are considered in this review only briefly. The NRG1 proteins play essential roles in the nervous system, heart, and breast. There is also evidence for involvement of NRG signaling in the development and function of several other organ systems, and in human disease, including the pathogenesis of schizophrenia and breast cancer. There are many NRG1 isoforms, raising the question "Why so many neuregulins?" Study of mice with targeted mutations ("knockout mice") has demonstrated that isoforms differing in their N-terminal region or in their epidermal growth factor (EGF)-like domain differ in their in vivo functions. These differences in function might arise because of differences in expression pattern or might reflect differences in intrinsic biological characteristics. While differences in expression pattern certainly contribute to the observed differences in in vivo functions, there are also marked differences in intrinsic characteristics that may tailor isoforms for specific signaling requirements, a theme that will be emphasized in this review. 相似文献
44.
Mandine E Gofflo D Jean-Baptiste V Sarubbi E Touyer G Deprez P Lesuisse D 《Journal of molecular recognition : JMR》2001,14(4):254-260
Various SH2 competitive binding assays, based on different techniques, have been described in the literature to identify and characterize SH2 ligands. The consideration that most reported methods show experimental limitations associated with assay parameters has prompted us to base our Src-SH2 inhibitor discovery program on the use of two different assays. In this study, two conceptually different biochemical methods designed to discover Src-SH2 inhibitors, respectively scintillation proximity assay (SPA) and surface plasmon resonance (SPR), have been evaluated and compared. For its high sensitivity and adaptability to automation SPA was chosen for high capacity screening (primary screen), whereas SPR was used for hits confirmation (secondary screening). However with the drastic improvement of inhibitor affinities, the limit of sensitivity was rapidly reached for the SPR assay based on the canonical pYEEI ligand. The substitution of the natural, monophosphorylated peptide ligand with a triphosphorylated peptide has allowed us to remarkably increase its sensitivity, so that molecules with nanomolar affinities could be easily differentiated in terms of IC(50) ranking. Such a new, improved SPR assay can be of great interest for the study of high affinity ligands of different SH2-based drug targets. 相似文献
45.
Valerio BertolasiAndrea Marchi Lorenza MarvelliRoberto Rossi Claudio Bianchini Isaac de los RiosMaurizio Peruzzini 《Inorganica chimica acta》2002,327(1):140-146
The reaction of the rhenium(V) nitrido complex [Re(N)Cl2(PPh3)2] with the tripodal ligand N(CH2CH2PPh2)3 (NP3) in THF gave [Re(N)Cl2(η2-P,P-NP3)] (1) in which NP3 acts as a tridentate ligand using the nitrogen and two phosphorus donors for coordination. Refluxing 1 in a polar solvent such as ethanol produced [(η4-NP3)Re(N)Cl]Cl (2) in which NP3 acts as a tetradentate ligand. Treatment of complex [Re(O)Cl3(AsPh3)2] containing the [ReO]3+ core with NP3 in THF yielded [ReCl3{η3-N,P,P-(N{CH2CH2Ph2}2{CH2CH2P(O)Ph2})}] (3). Complexes 1 and 3 have been characterized by single-crystal X-ray analyses. 相似文献
46.
The first complexes that contain the 2,6-bis(dicyclohexylphosphinomethyl)pyridine ligand (PNP) have been isolated and characterized. The reactions of K4Mo2Cl8, (n-Bu4N)2Re2Cl8 and PdBr2(1,5-COD) afford Mo2Cl4(PNP)(HPCy2) (1), ReCl3(PNP) (2) and PdBr2(PNP) (4), respectively, while from the reaction of PNP with cis-Re2(μ-O2CCH3)2Cl4(H2O)2 the heteromacrocylic dication [Cy2P{CH2pyCH2}2PCy2]2+ has been isolated as its mixed [Cl]−/[ReO4]− salt (3). The reaction of cis-Re2(μ-O2CCH3)2Cl4(H2O)2 with bis(diphenylphosphinomethyl)sulfide (PSP) gives the mononuclear Re(V) complex ReO(OEt)Cl2(PSP) (5) in which the S atom is not coordinated. The structures of 1-5 have been established by X-ray crystallography, that of 5 being the first for a complex of this ligand. 相似文献
47.
Camperi SA Iannucci NB Albanesi GJ Oggero Eberhardt M Etcheverrigaray M Messeguer A Albericio F Cascone O 《Biotechnology letters》2003,25(18):1545-1548
The peptide, Ala-Pro-Ala-Arg (APAR), was selected from the screening of a tetrapeptide combinatorial synthetic library as the ligand for affinity purification of an anti-Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) monoclonal antibody (Mab) developed in mouse ascitis. The affinity chromatographic matrix obtained by attachment of APAR to agarose, having a peptide density of 0.5 mol ml–1, showed a maximum capacity of 9.1 mg Mab ml–1 and a dynamic capacity of 3.9 mg Mab ml–1. A 95% yield of electrophoretically pure anti-GM-CSF was obtained in a single step. 相似文献
48.
Interleukin-1 (IL-1) has been implicated in neuroimmune responses and has pleiotropic actions in the brain. Compelling evidence
has shown that IL-1 is a major mediator of inflammation and the progression of cell death in response to brain injury and
cerebral ischemia. Its expression is strongly increased in these pathological conditions, and central administration of exogenous
IL-1 significantly exacerbates ischemic brain damage. In contrast, inhibiting IL-1 actions (by intracerebroventricular [icv]
injection of IL-1ra, neutralizing antibody to IL-1 or caspase-1 inhibitor) significantly reduces ischemic brain damage. IL-1
acts by binding to the IL-1 type-1 receptor (IL-1RI), which is to date, the only known functional receptor for IL-1. However,
our recent investigations suggest that IL-1 can act independently of IL-1RI, raising the possibility that additional, as yet
undiscovered, receptor(s) for IL-1 exist in the brain. The recent characterization of putative, new IL-1 ligands and new IL-1
receptor-related molecules leads to the hypothesis that there might be alternative IL-1 signaling pathway(s) in the central
nervous system (CNS). 相似文献
49.
Dirhodium(II) azetidinone-carboxylates are effective asymmetric catalysts for diazo decomposition of allyl diazoacetates and their subsequent intramolecular cyclopropanations. The effect of alkene substituents on enantiocontrol has been examined and modest selectivities have been achieved. Steric influences from substituents on the diazo carbon are seen to diminish enantioselectivities. 相似文献
50.
Delphine S. Dupuis Christiane Palmier Francis C. Colpaert Petrus J. Pauwels 《Journal of neurochemistry》1998,70(3):1258-1268
Abstract: G protein activation mediated by serotonin 5-HT1A and 5-HT1B/D receptors in guinea pig brain was investigated by using quantitative autoradiography of agonist-stimulated [35S]GTPγS binding to brain sections. [35S]GTPγS binding was stimulated by the mixed 5-HT1A/5-HT1B/D agonist L694247 in brain structures enriched in 5-HT1A binding sites, i.e., hippocampus (+140 ± 14%), dorsal raphe (+70 ± 8%), lateral septum (+52 ± 12%), cingulate (+36 ± 8%), and entorhinal cortex (+34 ± 5%). L694247 caused little or no stimulation of [35S]GTPγS binding in brain regions with high densities of 5-HT1B/D binding sites (e.g., substantia nigra, striatum, central gray, and dorsal subiculum). The [35S]GTPγS binding response was antagonized by WAY100635 (10 µM) and methiothepin (10 µM). In contrast, the 5-HT1B inverse agonist SB224289 (10 µM) did not affect the L694247-mediated [35S]GTPγS binding response, and the mixed 5-HT1B/D antagonist GR127935 (10 µM) yielded a partial blockade. The distribution pattern of the [35S]GTPγS binding response and the antagonist profile suggest the L694247-mediated response in guinea pig brain to be mediated by 5-HT1A receptors. In addition to L694247, 8-hydroxy-2-(di-n-propylamino)tetralin, and flesinoxan also stimulated [35S]GTPγS binding; their maximal responses varied between 46 and 52% compared with L694247, irrespective of the brain structure being considered. Sumatriptan, rizatriptan, and zolmitriptan (10 µM) stimulated [35S]GTPγS binding in the hippocampus by 20–50%. Naratriptan, CP122638, and dihydroergotamine stimulated [35S]GTPγS binding to a similar level as L694247 in hippocampus, lateral septum, and dorsal raphe. It appears that under the present experimental conditions, G protein activation through 5-HT1A but not 5-HT1B/D receptors can be measured in guinea pig brain sections. 相似文献