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991.
Body segment parameters are required when researching joint kinetics using inverse dynamics models. However, the only regression equations for estimating pediatric body segment parameters across a wide age range were developed, using photogrammetry, based on 12 boys and have not been validated to date (Jensen, R.K., 1986. Body segment mass, radius and radius of gyration proportions of children. Journal of Biomechanics 19, 359–368). To assess whether these equations could validly be applied to girls, we asked whether body segment parameters estimated by the equations differ from parameters measured using a validated magnetic resonance imaging (MRI) method. If so, do the differences cause significant differences in joint kinetics during normal gait? Body segment parameters were estimated from axial MRIs of the left thigh and shank of 10 healthy girls (9.6±0.9 years) and compared to those from Jensen's equations. Kinematics and kinetics were collected for 10 walking trials. Extrema in hip and knee moments and powers were compared between the two sets of body segment parameters. With the exception of the shank mass center and radius of gyration, body segment parameters measured using MRI were significantly different from those estimated using regression equations. These systematic differences in body segment parameters resulted in significant differences in sagittal-plane joint moments and powers during gait. Nevertheless, it is doubtful that even the greatest differences in kinetics are practically meaningful (0.3%BW×HT and 0.7%BW×HT/s for moments and power at the hip, respectively). Therefore, body segment parameters estimated using Jensen's regression equations are a suitable substitute for more detailed anatomical imaging of 8–10-year-old girls when quantifying joint kinetics during gait. 相似文献
992.
DSL ligand endocytosis physically dissociates Notch1 heterodimers before activating proteolysis can occur
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Nichols JT Miyamoto A Olsen SL D'Souza B Yao C Weinmaster G 《The Journal of cell biology》2007,176(4):445-458
Cleavage of Notch by furin is required to generate a mature, cell surface heterodimeric receptor that can be proteolytically activated to release its intracellular domain, which functions in signal transduction. Current models propose that ligand binding to heterodimeric Notch (hNotch) induces a disintegrin and metalloprotease (ADAM) proteolytic release of the Notch extracellular domain (NECD), which is subsequently shed and/or endocytosed by DSL ligand cells. We provide evidence for NECD release and internalization by DSL ligand cells, which, surprisingly, did not require ADAM activity. However, losses in either hNotch formation or ligand endocytosis significantly decreased NECD transfer to DSL ligand cells, as well as signaling in Notch cells. Because endocytosis-defective ligands bind hNotch, but do not dissociate it, additional forces beyond those produced through ligand binding must function to disrupt the intramolecular interactions that keep hNotch intact and inactive. Based on our findings, we propose that mechanical forces generated during DSL ligand endocytosis function to physically dissociate hNotch, and that dissociation is a necessary step in Notch activation. 相似文献
993.
White WH McCoy CM Meyer JA Winkle JR Plummer PR Kemper CJ Starkey R Snyder DE 《Journal of economic entomology》2007,100(1):155-163
The activity of spinosad, imidacloprid, and methomyl baits and technical actives were assessed against susceptible house flies, Musca domestica L. (Diptera: Muscidae). In a feeding assay, imidacloprid affected flies more rapidly than methomyl or spinosad, but spinosad was 2.7 times more potent than methomyl and 8 times more potent than imidacloprid. The profile of technical actives correlated with their respective fly bait formulations in laboratory assays. Although having the most rapid onset of activity in laboratory tests, up to 50% of flies remained alive after exposure to imidacloprid bait. In contrast, <5% of flies survived 24-h exposure to spinosad or methomyl baits. High temperature reduced the knockdown activity of imidacloprid bait and slowed the speed of kill for spinosad and methomyl baits over a 24-h exposure period. Spinosad and methomyl baits were also superior to imidacloprid when applied to the floors of environmentally controlled rooms at label recommended rates, providing good fly control for up to 21 d. The fact that a significant percentage of flies exposed to imidacloprid were rapidly knocked down but subsequently remained alive in all of the assays suggested that flies were recovering from initial exposure to this compound. Given its favorable safety profile, a high degree of initial and residual activity comparable with methomyl and lack of cross-resistance to other chemistries, spinosad bait may be a valuable component of house fly control programs to help control or delay the emergence of resistant populations. 相似文献
994.
Sheibani N Scheef EA Dimaio TA Wang Y Kondo S Sorenson CM 《Journal of cellular physiology》2007,210(3):616-625
Bcl-2 is the founding member of a family of proteins that influence apoptosis. During kidney development bcl-2 not only acts as a survival factor, but may also impact cell adhesive mechanisms and by extension branching morphogenesis. The interrelationship between cell adhesion, migration and apoptosis, important during development, is poorly understood. Here we examined the impact lack of bcl-2, an inhibitor of apoptosis, has on ureteric bud (UB) cell adhesion, migration, and branching morphogenesis. Bcl-2 -/- UB cells demonstrated increased cell migration, increased cell invasion and decreased adhesion to vitronectin and fibronectin compared with wild-type cells. Bcl-2 +/+ UB cells readily branched in collagen gel and Matrigel while bcl-2 -/- UB cells did not undergo significant branching in either matrix. Re-expression of bcl-2 in bcl-2 -/- UB cells restored their ability to undergo branching morphogenesis in Matrigel. Consistent with our in vitro data, we show that in the absence of bcl-2, embryonic kidneys undergo decreased UB branching. We observed decreased numbers of UB branch points, UB branch tips and a decreased distance to the first UB branch point in the absence of bcl-2. The alterations in bcl-2 -/- UB cell adhesion and migration was also associated with a significant alteration in expression of a number of extracellular matrix proteins. Bcl-2 -/- UB cells exhibited increased fibronectin expression and decreased thrombospondin-1 and osteopontin expression. Taken together, these data suggest that bcl-2 is required for the proper regulation of cell adhesive and migratory mechanisms, perhaps through modulation of the cellular microenvironment. 相似文献
995.
TetraploidMap for Windows: linkage map construction and QTL mapping in autotetraploid species 总被引:1,自引:0,他引:1
An earlier program, TetraploidMap, enabled linkage analysis to be performed for autotetraploid species, with a text-based input and output. The current program, TetraploidMap for Windows, is considerably enhanced, and now goes beyond linkage analysis to perform quantitative trait locus (QTL) interval mapping, with a range of models and thresholds assessed by permutation tests. A Windows-based interface facilitates data entry and exploration. TetraploidMap for Windows is freely available from the Web site of Bioinformatics and Statistics Scotland at http://www.bioss.ac.uk/ (user-friendly software). 相似文献
996.
Gamrekelashvili J Krüger C von Wasielewski R Hoffmann M Huster KM Busch DH Manns MP Korangy F Greten TF 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(3):1573-1580
The manner in which cells die is believed to have a major impact on the nature of immune responses to their released Ags. In this study, we present the first direct analysis of tumor-specific immune responses to in vivo occurring tumor cell death through apoptosis or necrosis. Mice bearing thymidine kinase-transfected tumors were treated either with ganciclovir to induce tumor cell apoptosis in vivo or a vascular targeting agent, ZD6126, to induce tumor cell necrosis in vivo. In contrast to tumor apoptosis, induction of necrosis reduced the frequency and impaired the function of tumor-specific CD8(+) T cells. Adoptive transfer of lymphocytes from mice with apoptotic tumors into tumor-challenged mice resulted in a significant tumor protection, which was absent when splenocytes were transferred from mice with necrotic tumors. Anti-CD40 treatment reversed impaired Ag-specific CD8(+) T cell responses in these mice. These observations have not only fundamental importance for the development of immunotherapy protocols but also help to understand the underlying mechanism of in vivo immune responses to tumor cell death. 相似文献
997.
Alpha interferon (IFN-alpha) and pegylated IFN-alpha (pegIFN-alpha) are used for the treatment of chronic hepatitis B (CHB). Unfortunately, only a minority of patients can be cured. The mechanisms responsible for hepatitis B virus (HBV) resistance to pegIFN-alpha treatment are not known. pegIFN-alpha is also used to treat patients with chronic hepatitis C (CHC). As with chronic hepatitis B, many patients with chronic hepatitis C cannot be cured. In CHC, IFN-alpha signaling has been found to be inhibited by an upregulation of protein phosphatase 2A (PP2A). PP2A inhibits protein arginine methyltransferase 1 (PRMT1), the enzyme that catalyzes the methylation of the important IFN-alpha signal transducer STAT1. Hypomethylated STAT1 is less active because it is bound by its inhibitor, PIAS1. In the present work, we investigated whether similar molecular mechanisms are also responsible for the IFN-alpha resistance found in many patients with chronic hepatitis B. We analyzed the expression of PP2A, the enzymatic activity of PRMT1 (methylation assays), the phosphorylation and methylation of STAT1, the association of STAT1 with PIAS1 (via coimmunoprecipitation assays), the binding of activated STAT1 to interferon-stimulated response elements (via electrophoretic mobility shift assays), and the induction of interferon target genes (via real-time RT-PCR) in human hepatoma cells expressing HBV proteins as well as in liver biopsies from patients with chronic hepatitis B and from controls. We found an increased expression of PP2A and an inhibition of IFN-alpha signaling in cells expressing HBV proteins and in liver biopsies of patients with CHB. The molecular mechanisms involved are similar to those found in chronic hepatitis C. 相似文献
998.
Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection 总被引:1,自引:0,他引:1
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Larrea E Riezu-Boj JI Gil-Guerrero L Casares N Aldabe R Sarobe P Civeira MP Heeney JL Rollier C Verstrepen B Wakita T Borrás-Cuesta F Lasarte JJ Prieto J 《Journal of virology》2007,81(7):3662-3666
Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by CTLA-4-expressing T cells and constitutes an important mediator of peripheral immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication expressed higher levels of IDO mRNA than noninfected cells when stimulated with gamma interferon or when cocultured with activated T cells. In infected chimpanzees, hepatic IDO expression decreased in animals that cured the infection, while it remained high in those that progressed to chronicity. For both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated directly. Induction of IDO may dampen T-cell reactivity to viral antigens in chronic HCV infection. 相似文献
999.
1000.
Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1
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Moza B Varma AK Buonpane RA Zhu P Herfst CA Nicholson MJ Wilbuer AK Seth NP Wucherpfennig KW McCormick JK Kranz DM Sundberg EJ 《The EMBO journal》2007,26(4):1187-1197
Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor beta chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC-SAG-TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity. 相似文献