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341.
342.
Philippe GAC Vanden Bergh Thomas Fett Laurent LM Zecchinon Anne VT Thomas Daniel JM Desmecht 《BMC veterinary research》2005,1(1):1-7
Background
Lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18, alphaLbeta2), the most abundant and widely expressed beta2-integrin, is required for many cellular adhesive interactions during the immune response. Many studies have shown that LFA-1 is centrally involved in the pathogenesis of several diseases caused by Repeats-in-toxin (RTX) -producing bacteria. 相似文献343.
344.
Nociceptin/orphanin FQ (N/OFQ) and nocistatin are two neuropeptides originated from the same precursor prepronociceptin/orphanin FQ (ppN/OFQ). N/OFQ is the endogenous ligand of the NOP receptor, while the target of action of nocistatin is still unknown. N/OFQ modulates various biological functions, including anxiety. Conversely, nocistatin either behaves as a functional N/OFQ antagonist or evokes per se effects opposite to those of N/OFQ. Here we investigated the interaction between the anxiolytic-like effects of N/OFQ and the anxiogenic-like action of nocistatin with those evoked by GABAA receptor ligands in the mouse elevated plus maze. The anxiogenic-like effects of the GABAA receptor antagonist pentylenetetrazol (20 mg/kg; intraperitoneal, i.p.) were abolished by the co-treatment with N/OFQ (10 pmol; intracerebroventricular, i.c.v.) while potentiated by the administration of nocistatin (0.01 pmol; i.c.v.). The anxiolytic-like effects of the benzodiazepine receptor agonist diazepam (0.75 mg/kg, i.p.) were reversed by nocistatin (0.1 pmol; i.c.v.), whereas signs of sedation were observed when mice were co-treated with diazepam and N/OFQ (3 pmol). Interesting enough, the i.p. treatment with flumazenil (1 mg/kg) blocked the anxiolytic-like effects of N/OFQ (10 pmol; i.c.v.), but not the anxiogenic effect elicited by nocistatin. Collectively, our findings suggest that the effects on anxiety elicited by pentylenetetrazol and diazepam can be counteracted or potentiated in the presence of N/OFQ and nocistatin. In addition, the effects on anxiety of N/OFQ, but not nocistatin, appear to be dependent on the benzodiazepine site of the GABAA receptor. 相似文献
345.
346.
Rieke Alten Hermann Gram Leo A Joosten Bvanden Wim Berg Joachim Sieper Siegfrid Wassenberg Gerd Burmester Piet van Riel Maria Diaz-Lorente Gerardus JM Bruin Thasia G Woodworth Christiane Rordorf Yannik Batard Andrew M Wright Thomas Jung 《Arthritis research & therapy》2008,10(3):1-9
Introduction
IL-1β is a proinflammatory cytokine driving joint inflammation as well as systemic signs of inflammation, such as fever and acute phase protein production.Methods
ACZ885, a fully human monoclonal antibody that neutralizes the bioactivity of human IL-1β, was generated to study the potent and long-lasting neutralization of IL-1β in mechanistic animal models as well as in a proof-of-concept study in patients with rheumatoid arthritis (RA).Results
The mouse IL-1 receptor cross-reacts with human IL-1β, and it was demonstrated that ACZ885 can completely suppress IL-1β-mediated joint inflammation and cartilage destruction in mice. This observation prompted us to study the safety, tolerability and pharmacodynamic activity of ACZ885 in RA patients in a small proof-of-concept study – the first to be conducted in humans. Patients with active RA despite treatment with stable doses of methotrexate were enrolled in this dose escalation study. The first 32 patients were split into four cohorts of eight patients each (six were randomly assigned to active treatment and two to placebo). ACZ885 doses were 0.3, 1, 3 and 10 mg/kg, administered intravenously on days 1 and 15. To explore efficacy within 6 weeks of treatment, an additional 21 patients were randomly assigned to the 10 mg/kg cohort, resulting in a total of 20 patients dosed with 10 mg/kg and 15 patients treated with placebo. There was clinical improvement (American College of Rheumatology 20% improvement criteria) at week 6 in the 10 mg/kg treatment group; however, this did not reach statistical significance (P = 0.085). A statistically significant reduction in disease activity score was observed after 4 weeks in the 10 mg/kg group. Onset of action was rapid, because most responders exhibited improvement in their symptoms within the first 3 weeks. C-reactive protein levels decreased in patients treated with ACZ885 within 1 week. ACZ885 was well tolerated. Three patients receiving ACZ885 developed infectious episodes that required treatment. No anti-ACZ885 antibodies were detected during the study.Conclusion
ACZ885 administration to methotrexate-refractory patients resulted in clinical improvement in a subset of patients. Additional studies to characterize efficacy in RA and to determine the optimal dose regimen appear warranted.Trial Registration
ClinicalTrials.gov identifier NCT00619905. 相似文献347.
348.
Marc Beyer Hongwei Wang Nina Peters Sandra Doths Cordula Koerner-Rettberg Peter JM Openshaw Jürgen Schwarze 《Respiratory research》2005,6(1):70
Background
The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV).Methods
Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c+ CD8+ and CD11c- CD8+ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8+ T cells was assessed by quantitative PCR.Results
Following RSV infection CD11c+ CD8+ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8+ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8+ T cells in the absence of RSV infection, its mRNA was expressed in CD8+ T cells of both naïve and RSV infected mice. CD11c+, but not CD11c-, CD8+ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c+ CD8+ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo.Conclusion
CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo. 相似文献349.
Camarda V Rizzi A Calo G Wirth K Regoli D 《Canadian journal of physiology and pharmacology》2002,80(4):281-286
Peptide and nonpeptide compounds have been shown to interact specifically with B2 receptors of three different species, namely human, rabbit, and pig. Peptide agonists and nonpeptide antagonists show marked differences in potencies and suggest the existence of B2 receptor subtypes. This conclusion is based on data obtained with the modified agonist peptide LF 150943 whose potency (pEC50 9.4) is at least 100-fold higher in rabbit than in humans (7.4) and pig (6.7). The same conclusion can be drawn from data obtained with antagonists that are more potent in humans (LF 160687, pA2 9.2) than in rabbit (8.7) and pig (8.2) or with antagonists (S 1567) that show the opposite potency order, being much weaker in humans (pA2 6.9) than in rabbit (7.6) and pig (9.4). Two other compounds (FR 173657 and FR 172357) show similar pharmacological spectra as S 1567 and differ from LF 160687. 相似文献
350.
Recently, the cloning of a novel preprotachykinin gene (PPT-C) has been reported. This gene codes for a novel peptide named hemokinin 1 (HK-1). In contrast with the known tachykinins, which are exclusively expressed in neuronal tissues, PPT-C mRNA was detected primarily in hematopoietic cells. In this study, we pharmacologically characterised the effects of HK-1 using three tachykinin monoreceptor systems, namely the rabbit jugular vein (rbJV) for NK(1), the rabbit pulmonary artery (rbPA) for NK(2), and rat portal vein (rPV) for NK(3) receptors. In all these preparations substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) elicited concentration dependent contractions showing similar maximal effects and the following rank order of potency: SP > NKA = NKB in the rbJV, NKA > NKB > SP in the rbPA, and NKB > NKA > SP in the rPV. In those vessels HK-1 behaved as a full agonist displaying potencies similar (rbPA and rPV) or slightly higher (rbJV) than those of SP. In the rbJV, SR 140333, a selective NK(1) receptor antagonist, antagonised the effects of HK-1 and SP with similar high potencies (pK(B) 9.3 and 9.5, respectively). Similar results were obtained with the pseudopeptide NK(1) antagonist, MEN 11467 (pK(B) 8.8 and 8.6, respectively). Taken together, these data indicate that HK-1 behaves as a NK(1) preferring receptor agonist. 相似文献