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Neuroproteomics: Expression Profiling of the Brain's Proteomes in Health and Disease 总被引:6,自引:0,他引:6
Kim SI Voshol H van Oostrum J Hastings TG Cascio M Glucksman MJ 《Neurochemical research》2004,29(6):1317-1331
The term "proteome" describes the protein complement of a genome. Proteomes of cells are dynamic and are directly affected by environmental factors, such as stress and/or drug treatment, or as a result of aging and disease. One of the distinct advantages of proteomic analysis, not attainable with RNA expression data, is the ability to fractionate the cell's proteins into various subpopulations. In neuroscience, "neuromics" (proteomics in the central nervous system) is in its infancy, with a paucity of studies in the context of the brain. One of the objectives of this review is to illustrate the potential of neuromics to profile differences in the distribution of thousands of proteins as a function of disease markers. We have previously used this approach to determine the effects of varied postmortem interval in examining human brain tissue and to identify biomarkers. Here we review proteomic studies of schizophrenia, Alzheimer's disease, and Parkinson's disease. Experimental results regarding Parkinson's disease are presented to illustrate the potential of neuromics to identify pathways of pathogenesis and novel therapeutic targets. 相似文献
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Lowe DB Magnuson S Qi N Campbell AM Cook J Hong Z Wang M Rodriguez M Achebe F Kluender H Wong WC Bullock WH Salhanick AI Witman-Jones T Bowling ME Keiper C Clairmont KB 《Bioorganic & medicinal chemistry letters》2004,14(12):3155-3159
A series of (5-(2H)-isoxazolonyl) ureas were developed as nanomolar inhibitors of hormone-sensitive lipase, an enzyme of potential importance in the treatment of diabetes. 相似文献
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The activation, proliferation, differentiation, and trafficking of CD4 T cells is central to the development of type I immune responses. MHC class II (MHCII)-bearing dendritic cells (DCs) initiate CD4(+) T cell priming, but the relative contributions of other MHCII(+) APCs to the complete Th1 immune response is less clear. To address this question, we examined Th1 immunity in a mouse model in which I-A(beta)(b) expression was targeted specifically to the DCs of I-A(beta)b-/- mice. MHCII expression is reconstituted in CD11b(+) and CD8alpha(+) DCs, but other DC subtypes, macrophages, B cells, and parenchymal cells lack of expression of the I-A(beta)(b) chain. Presentation of both peptide and protein Ags by these DC subsets is sufficient for Th1 differentiation of Ag-specific CD4(+) T cells in vivo. Thus, Ag-specific CD4(+) T cells are primed to produce Th1 cytokines IL-2 and IFN-gamma. Additionally, proliferation, migration out of lymphoid organs, and the number of effector CD4(+) T cells are appropriately regulated. However, class II-negative B cells cannot receive help and Ag-specific IgG is not produced, confirming the critical MHCII requirement at this stage. These findings indicate that DCs are not only key initiators of the primary response, but provide all of the necessary cognate interactions to control CD4(+) T cell fate during the primary immune response. 相似文献
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Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodeficiency virus-infected adults 总被引:12,自引:0,他引:12
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Barbour JD Wrin T Grant RM Martin JN Segal MR Petropoulos CJ Deeks SG 《Journal of virology》2002,76(21):11104-11112
Continued use of antiretroviral therapy despite the emergence of drug-resistant human immunodeficiency virus (HIV) has been associated with the durable maintenance of plasma HIV RNA levels below pretherapy levels. The factors that may account for this partial control of viral replication were assessed in a longitudinal observational study of 20 HIV-infected adults who remained on a stable protease inhibitor-based regimen despite ongoing viral replication (plasma HIV RNA levels consistently >500 copies/ml). Longitudinal plasma samples (n = 248) were assayed for drug susceptibility and viral replication capacity (measured by using a single-cycle recombinant-virus assay). The initial treatment-mediated decrease in plasma viremia was directly proportional to the reduction in replicative capacity (P = 0.01). Early virologic rebound was associated the emergence of a virus population exhibiting increased protease inhibitor phenotypic resistance, while replicative capacity remained low. During long-term virologic failure, plasma HIV RNA levels often remained stable or increased slowly, while phenotypic resistance continued to increase and replicative capacity decreased slowly. The emergence of primary genotypic mutations within protease (particularly V82A, I84V, and L90M) was temporally associated with increasing phenotypic resistance and decreasing replicative capacity, while the emergence of secondary mutations within protease was associated with more-gradual changes in both phenotypic resistance and replicative capacity. We conclude that HIV may be constrained in its ability to become both highly resistant and highly fit and that this may contribute to the continued partial suppression of plasma HIV RNA levels that is observed in some patients with drug-resistant viremia. 相似文献
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Attwood TK 《Briefings in bioinformatics》2002,3(3):252-263
The PRINTS database houses a collection of protein fingerprints, which may be used to assign family and functional attributes to uncharacterised sequences, such as those currently emanating from the various genome-sequencing projects. The April 2002 release includes 1,700 family fingerprints, encoding approximately 10,500 motifs, covering a range of globular and membrane proteins, modular polypeptides and so on. Fingerprints are groups of conserved motifs that, taken together, provide diagnostic protein family signatures. They derive much of their potency from the biological context afforded by matching motif neighbours; this makes them at once more flexible and powerful than single-motif approaches. The technique further departs from other pattern-matching methods by readily allowing the creation of fingerprints at superfamily-, family- and subfamily-specific levels, thereby allowing more fine-grained diagnoses. Here, we provide an overview of the method of protein fingerprinting and how the results of fingerprint analyses are used to build PRINTS and its relational cousin, PRINTS-S. 相似文献
29.
Mulder NJ Apweiler R Attwood TK Bairoch A Bateman A Binns D Biswas M Bradley P Bork P Bucher P Copley R Courcelle E Durbin R Falquet L Fleischmann W Gouzy J Griffith-Jones S Haft D Hermjakob H Hulo N Kahn D Kanapin A Krestyaninova M Lopez R Letunic I Orchard S Pagni M Peyruc D Ponting CP Servant F Sigrist CJ;InterPro Consortium 《Briefings in bioinformatics》2002,3(3):225-235
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Microarray profile of differentially expressed genes in a monkey model of allergic asthma 总被引:2,自引:1,他引:1
Zou J Young S Zhu F Gheyas F Skeans S Wan Y Wang L Ding W Billah M McClanahan T Coffman RL Egan R Umland S 《Genome biology》2002,3(5):research0020.1-research002013