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181.
Huang Y Norton DD Precht P Martindale JL Burkhardt JK Wange RL 《The Journal of biological chemistry》2005,280(25):23576-23583
ADAP (adhesion and degranulation-promoting adaptor protein) and SKAP55 (Src kinase-associated phosphoprotein of 55 kDa) are T cell adaptors that mediate inside-out signaling from the T cell antigen receptor to integrins, giving rise to increased integrin affinity/avidity and formation of the immunological synapse between the T cell and the antigen-presenting cell. These two proteins are tightly and constitutively associated with one another, and their ability to interact is required for inside-out signaling. Here we show in an ADAP-deficient Jurkat T cell line that the co-dependence of ADAP and SKAP55 extends beyond their functional and physical interactions and show that SKAP55 protein is unstable in the absence of ADAP. Restoration of ADAP to the ADAP-deficient Jurkat T cell line restores SKAP55 expression by causing a 5-fold decrease in the rate of SKAP55 proteolysis. Inactivation of the Src homology 3 domain of SKAP55, which mediates the association between SKAP55 with ADAP, blocks the protective effect of ADAP. The half-life of SKAP55, in the absence of ADAP, is approximately 15-20 min, increasing to 90 min in the presence of ADAP. This is a remarkably rapid rate of turnover for a signaling protein and suggests the possibility that stimuli that signal for the stabilization of SKAP55 may play an important role in T cell adhesion and conjugate formation. 相似文献
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185.
Samuel J. Vidal S. Aidan Quinn Janis de la Iglesia-Vicente Dennis M. Bonal Veronica Rodriguez-Bravo Adolfo Firpo-Betancourt Carlos Cordon-Cardo Josep Domingo-Domenech 《Journal of visualized experiments : JoVE》2014,(85)
The cancer stem cell (CSC) model has been considerably revisited over the last two decades. During this time CSCs have been identified and directly isolated from human tissues and serially propagated in immunodeficient mice, typically through antibody labeling of subpopulations of cells and fractionation by flow cytometry. However, the unique clinical features of prostate cancer have considerably limited the study of prostate CSCs from fresh human tumor samples. We recently reported the isolation of prostate CSCs directly from human tissues by virtue of their HLA class I (HLAI)-negative phenotype. Prostate cancer cells are harvested from surgical specimens and mechanically dissociated. A cell suspension is generated and labeled with fluorescently conjugated HLAI and stromal antibodies. Subpopulations of HLAI-negative cells are finally isolated using a flow cytometer. The principal limitation of this protocol is the frequently microscopic and multifocal nature of primary cancer in prostatectomy specimens. Nonetheless, isolated live prostate CSCs are suitable for molecular characterization and functional validation by transplantation in immunodeficient mice. 相似文献
186.
Ingmar Sch?fer Marc Pawels Claudia Küver Nadine Janis Pohontsch Martin Scherer Hendrik van den Bussche Hanna Kaduszkiewicz 《PloS one》2014,9(4)
Objective
Diabetes mellitus is highly prevalent and can lead to serious complications and mortality. Patient education can help to avoid negative outcomes, but up to half of the patients do not participate. The aim of this study was to analyze patients'' attitudes towards diabetes education in order to identify barriers to participation and develop strategies for better patient education.Methods
We conducted a qualitative study. Seven GP practices were purposively selected based on socio-demographic data of city districts in Hamburg, Germany. Study participants were selected by their GPs in order to increase participation. Semi-structured face-to-face interviews were conducted with 14 patients. Interviews were audiotaped and transcribed verbatim. The sample size was determined by data saturation. Data were analysed by qualitative content analysis. Categories were determined deductively and inductively.Results
The interviews yielded four types of barriers: 1) Statements and behaviour of the attending physician influence the patients'' decisions about diabetes education. 2) Both, a good state of health related to diabetes and physical/psychosocial comorbidity can be reasons for non-participation. 3) Manifold motivational factors were discussed. They ranged from giving low priority to diabetes to avoidance of implications of diabetes education as being confronted with illness narratives of others. 4) Barriers also include aspects of the patients'' knowledge and activity.Conclusions
First, physicians should encourage patients to participate in diabetes education and argue that they can profit even if actual treatment and examination results are promising. Second, patients with other priorities, psychic comorbidity or functional limitations might profit more from continuous individualized education adapted to their specific situation instead of group education. Third, it might be justified that patients do not participate in diabetes education if they have slightly increased blood sugar values only and no risk for harmful consequences or if they already have sufficient knowledge on diabetes. 相似文献187.
Janis Jansons James Stattel Annalisa Verri Joseph Gambino Naseema Khan Federico Focher 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):669-682
Abstract N2-(p-n-Octylphenyl)-2′-deoxyguanosine 5′-triphosphate (OctPdGTP)has been synthesized chemically. OctPdGTP inhibited DNA polymerases (pol) α, δ and ε from calf thymus, with moderate selectivity for pol α. Mechanistic studies on pol α and bacteriophage T4 DNA polymerase revealed competitive and mixed kinetics of OctPdGTP with respect to the substrate dGTP when the enzymes were assayed on activated DNA and oligo dT:poly dA, respectively. 相似文献
188.
Octavio A. Gonzalez M. John Novak Sreenatha Kirakodu Arnold J. Stromberg Shu Shen Luis Orraca Janis Gonzalez-Martinez Jeffrey L. Ebersole 《Apoptosis : an international journal on programmed cell death》2013,18(3):249-259
Apoptotic processes are important for physiologic renewal of an intact epithelial barrier and contribute some antimicrobial resistance for bacteria and viruses, as well as anti-inflammatory effects that benefits the mucosa. The oral cavity presents a model of host-bacterial interactions at mucosal surfaces, in which a panoply of microorganisms colonizes various niches in the oral cavity and creates complex multispecies biofilms that challenge the gingival tissues. This report details gene expression in apoptotic pathways that occur in oral mucosal tissues across the lifespan, using a nonhuman primate model. Macaca mulatta primates from 2 to 23 years of age (n = 23) were used in a cross-sectional study to obtain clinical healthy gingival tissues specimens. Further, mRNA was prepared and evaluated using the Affymetrix Rhesus GeneChip and 88 apoptotic pathway genes were evaluated. The results identified significant positive correlations with age in 12 genes and negative correlations with an additional five genes. The gene effects were predicted to alter apoptosis receptor levels, extrinsic apoptotic pathways through caspases, cytokine effects on apoptotic events, Ca+2-induced death signaling, cell cycle checkpoints, and potential effects of survival factors. Both the positively and negatively correlated genes within the apoptotic pathways provided evidence that healthy tissues in aging animals exhibit decreased apoptotic potential compared to younger animals. The results suggested that decreased physiologic apoptotic process in the dynamic septic environment of the oral mucosal tissues could increase the risk of aging tissues to undergo destructive disease processes through dysregulated inflammatory responses to the oral microbial burden. 相似文献
189.
Georges Limbert John Middleton Janis Laizans Modris Dobelis Ivar Knets 《Computer methods in biomechanics and biomedical engineering》2013,16(5-6):337-345
This study describes the development of a constitutive law for the modelling of the periodontal ligament (PDL) and its practical implementation into a commercial finite element code. The constitutive equations encompass the essential mechanical features of this biological soft tissue: non-linear behaviour, large deformations, anisotropy, distinct behaviour in tension and compression and the fibrous characteristics. The approach is based on the theory of continuum fibre-reinforced composites at finite strain where a compressible transversely isotropic hyperelastic strain energy function is defined. This strain energy density function is further split into volumetric and deviatoric contributions separating the bulk and shear responses of the material. Explicit expressions of the stress tensors in the material and spatial configurations are first established followed by original expressions of the elasticity tensors in the material and spatial configurations. As a simple application of the constitutive model, two finite element analyses simulating the mechanical behaviour of the PDL are performed. The results highlight the significance of integrating the fibrous architecture of the PDL as this feature is shown to be responsible for the complex strain distribution observed. 相似文献
190.
Tanner F. Robertson Pragati Chengappa Daniela Gomez Atria Christine F. Wu Lyndsay Avery Nathan H. Roy Ivan Maillard Ryan J. Petrie Janis K. Burkhardt 《The Journal of cell biology》2021,220(6)
Ezrin, radixin, and moesin (ERM) family proteins regulate cytoskeletal responses by tethering the plasma membrane to the underlying actin cortex. Mutations in ERM proteins lead to severe combined immunodeficiency, but the function of these proteins in T cells remains poorly defined. Using mice in which T cells lack all ERM proteins, we demonstrate a selective role for these proteins in facilitating S1P-dependent egress from lymphoid organs. ERM-deficient T cells display defective S1P-induced migration in vitro, despite normal responses to standard protein chemokines. Analysis of these defects revealed that S1P promotes a fundamentally different mode of migration than chemokines, characterized by intracellular pressurization and bleb-based motility. ERM proteins facilitate this process, controlling directional migration by limiting blebbing to the leading edge. We propose that the distinct modes of motility induced by S1P and chemokines are specialized to allow T cell migration across lymphatic barriers and through tissue stroma, respectively. 相似文献