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991.
The rodent filaria Litomosoides sigmodontis harbour Wolbachia, endosymbionts essential for worm embryogenesis, larval development and adult survival. To study the effect of tetracycline, which depletes Wolbachia, on the development of microfilariae (L1s, MF) to L3 in the intermediate host Ornithonyssus bacoti, and to observe the development of Wolbachia-depleted L3s in Mongolian gerbils (Meriones unguiculatus); microfilaremic gerbils were treated orally with tetracycline for 6 weeks (primary infected (1°) Tet) or untreated (1° Con). Treatment resulted in a significant reduction of Wolbachia per MF in 1° Tet gerbils. Naïve mites then fed on the 1° Tet and 1° Con gerbils in the week after treatment ended, when MF levels were not significantly different, and used to infect new gerbils (secondary infected (2°) Tet, 2° Con) via natural infection. The infection rate from dissected mites was 9% and 54% (1° Tet and 1° Con, respectively). After 3 months, worms were isolated from 2° gerbils. Significantly fewer female worms developed in 2° Tet gerbils. In contrast, there was no difference in the number of male worms that developed in 2° gerbils, resulting in a male biased sex-ratio. Although 2° Tet male worms had fewer Wolbachia than 2° Con males, development was not impaired. Female worms that developed from Wolbachia-depleted MF had Wolbachia levels equivalent to worms from 2° Con animals. Thus, tetracycline pre-treatment selected for female worms with high numbers of Wolbachia, whereas male worms had median Wolbachia levels significantly lower than 2° Con males. Therefore, female worms require a higher threshold of Wolbachia for their development. The worms analysed were only exposed to tetracycline as MF, ruling out direct effects of tetracycline during larval development in the mites or 2° gerbils, suggesting that the depletion of Wolbachia in MF was the cause of impaired larval development. 相似文献
992.
Priya Sakthivel Marcus Gereke Angele Breithaupt Dietmar Fuchs Luca Gigliotti Achim D. Gruber Umberto Dianzani Dunja Bruder 《PloS one》2014,9(7)
Inducible Co-stimulator (ICOS) plays a critical role in mediating T cell differentiation and function and is considered a key player in balancing T effector and T regulatory (Treg) cell responses. Here we show that activation of the ICOS signalling pathway during acute influenza A virus (IAV) infection by application of an agonistic ICOS antibody reduced the frequency of CD8+ T cells in the respiratory tract of IAV infected animals and delayed pathogen elimination. In line with this, immune-mediated influenza pneumonia was significantly ameliorated in mice that received ICOS agonist as indicated by significantly reduced alveolar infiltrations and bronchointerstitial pneumonia, while at the same time virus-related pathology remained unaffected. Importantly, ICOS agonist treatment resulted in expansion of CD4+Foxp3+ Tregs in IAV infected mice, which was associated with elevated levels of the immunosuppressive cytokine IL-10 in the alveolar space. Together, our findings suggest a prominent role of ICOS signaling during acute IAV infection by increasing the Treg/CD8+ T cell ratio with beneficial outcome on immune-mediated pneumonia and underline the suitability of ICOS as potential therapeutic target for immune intervention in those infectious conditions characterized by strong immunopathology rather than virus-mediated cytopathic effects. 相似文献
993.
Martin L. Daus Katja Wagenführ Achim Thomzig Susann Boerner Peter Hermann Antje Hermelink Michael Beekes Peter Lasch 《The Journal of biological chemistry》2013,288(49):35068-35080
The self-replicative conformation of misfolded prion proteins (PrP) is considered a major determinant for the seeding activity, infectiousness, and strain characteristics of prions in different host species. Prion-associated seeding activity, which converts cellular prion protein (PrPC) into Proteinase K-resistant, infectious PrP particles (PrPTSE), can be monitored in vitro by protein misfolding cyclic amplification (PMCA). Thus, PMCA has been established as a valuable analytical tool in prion research. Currently, however, it is under discussion whether prion strain characteristics are preserved during PMCA when parent seeds are amplified in PrPC substrate from the identical host species. Here, we report on the comparative structural analysis of parent and progeny (PMCA-derived) PrP seeds by an improved approach of sensitive infrared microspectroscopy. Infrared microspectroscopy revealed that PMCA of native hamster 263K scrapie seeds in hamster PrPC substrate caused conformational alterations in progeny seeds that were accompanied by an altered resistance to Proteinase K, higher sedimentation velocities in gradient ultracentrifugations, and a longer incubation time in animal bioassays. When these progeny seeds were propagated in hamsters, misfolded PrP from brain extracts of these animals showed mixed spectroscopic and biochemical properties from both parental and progeny seeds. Thus, strain modifications of 263K prions induced by PMCA seem to have been partially reversed when PMCA products were reinoculated into the original host species. 相似文献
994.
Global self-esteem was tested to predict quicker cardiovascular adaptation during stressful oral thesis presentation and faster
habituation from the first to the second and third thesis presentations. Nineteen graduate students initially rated their
global self-esteem and afterwards orally presented their theses proposals in 20-min presentations to their thesis supervisor
and peers. A second and third presentation of the revised thesis concepts took place at 4-weeks intervals. Ambulatory blood
pressure and heart rate were assessed repeatedly during the presentations. Post-talk self ratings of stressfulness indicated
presentations to be a strong public speaking stressor. One hundred and thirty-eight measurements of systolic (SBP), diastolic
blood pressure (DBP), and heart rate (HR) showed a significant adaptation (decrease) during presentations. There was an overall
mean level decrease from the first to the second, and the second to the third presentations in HR, but not in SBP and DBP.
However, habituation in SBP and DBP across three presentations was significantly faster (p < .05) in those participants who initially reported higher levels of global self-esteem. Higher global self-esteem did not
foster adaptation within the presentations. Self-esteem is discussed as an important individual resource that allows successful
coping with recurring evaluative threats. 相似文献
995.
Katrin H?gner Thorsten Wolff Stephan Pleschka Stephanie Plog Achim D. Gruber Ulrich Kalinke Hans-Dieter Walmrath Johannes Bodner Stefan Gattenl?hner Peter Lewe-Schlosser Mikhail Matrosovich Werner Seeger Juergen Lohmeyer Susanne Herold 《PLoS pathogens》2013,9(2)
Influenza viruses (IV) cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using ex vivo and in vivo IV infection models, we demonstrate that alveolar macrophage (AM)-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL). Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR-) and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury. 相似文献
996.
Mapping of gene loci for nephronophthisis type 4 and Senior-Løken syndrome, to chromosome 1p36 下载免费PDF全文
Schuermann MJ Otto E Becker A Saar K Rüschendorf F Polak BC Ala-Mello S Hoefele J Wiedensohler A Haller M Omran H Nürnberg P Hildebrandt F 《American journal of human genetics》2002,70(5):1240-1246
For nephronophthisis (NPHP), the primary genetic cause of chronic renal failure in young adults, three loci have been mapped. To identify a new locus for NPHP, we here report on total-genome linkage analysis in seven families with NPHP, in whom we had excluded linkage to all three known NPHP loci. LOD scores >1 were obtained at nine loci, which were then fine mapped at 1-cM intervals. Extensive total-genome haplotype analysis revealed homozygosity in one family, in the region of the PCLN1 gene. Subsequent mutational analysis in this gene revealed PCLN1 mutations, thereby allowing exclusion of this family as a phenocopy. Multipoint linkage analysis for the remaining six families with NPHP together yielded a maximum LOD score (Zmax) of 8.9 (at D1S253). We thus identified a new locus, NPHP4, for nephronophthisis. Markers D1S2660 and D1S2642 are flanking NPHP4 at a 2.9-cM critical interval. In one family with NPHP4, extensive genealogical studies were conducted, revealing consanguinity during the 17th century. On the basis of haplotype sharing by descent, we obtained a multipoint Zmax of 5.8 for D1S253 in this kindred alone. In addition, we were able to localize to the NPHP4 locus a new locus for Senior-Løken syndrome, an NPHP variant associated with retinitis pigmentosa. 相似文献
997.
Bippes CC Feldmann A Stamova S Cartellieri M Schwarzer A Wehner R Schmitz M Rieber EP Zhao S Schäkel K Temme A Scofield RH Kurien BT Bartsch H Bachmann M 《PloS one》2011,6(1):e16315
Background
Previously, we identified a major myeloid-derived proinflammatory subpopulation of human blood dendritic cells which we termed slanDCs (e.g. Schäkel et al. (2006) Immunity 24, 767–777). The slan epitope is an O-linked sugar modification (6-sulfo LacNAc, slan) of P-selectin glycoprotein ligand-1 (PSGL-1). As slanDCs can induce neoantigen-specific CD4+ T cells and tumor-reactive CD8+ cytotoxic T cells, they appear as promising targets for an in vivo delivery of antigens for vaccination. However, tools for delivery of antigens to slanDCs were not available until now. Moreover, it is unknown whether or not antigens delivered via the slan epitope can be taken up, properly processed and presented by slanDCs to T cells.Methodology/Principal Findings
Single chain fragment variables were prepared from presently available decavalent monoclonal anti-slan IgM antibodies but failed to bind to slanDCs. Therefore, a novel multivalent anti-slanDC scaffold was developed which consists of two components: (i) a single chain bispecific recombinant diabody (scBsDb) that is directed on the one hand to the slan epitope and on the other hand to a novel peptide epitope tag, and (ii) modular (antigen-containing) linker peptides that are flanked at both their termini with at least one peptide epitope tag. Delivery of a Tetanus Toxin-derived antigen to slanDCs via such a scBsDb/antigen scaffold allowed us to recall autologous Tetanus-specific memory T cells.Conclusions/Significance
In summary our data show that (i) the slan epitope can be used for delivery of antigens to this class of human-specific DCs, and (ii) antigens bound to the slan epitope can be taken up by slanDCs, processed and presented to T cells. Consequently, our novel modular scaffold system may be useful for the development of human vaccines. 相似文献998.
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