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1.
Allicin inhibits SDF-1alpha-induced T cell interactions with fibronectin and endothelial cells by down-regulating cytoskeleton rearrangement, Pyk-2 phosphorylation and VLA-4 expression 总被引:2,自引:0,他引:2 下载免费PDF全文
Sela U Ganor S Hecht I Brill A Miron T Rabinkov A Wilchek M Mirelman D Lider O Hershkoviz R 《Immunology》2004,111(4):391-399
Allicin, a major ingredient of fresh garlic extract that is produced during the crushing of garlic cloves, exerts various beneficial biological effects, including a broad spectrum of antimicrobial activity, antihyperlipidaemic and antihypertensive effects. However, how allicin affects the immune system is less well known, and its effect on human T cells has never been studied. Here, we examined the in-vitro effects of allicin on the functioning of T cells related to their entry to inflamed extravascular sites. We found that allicin (20-100 microm) inhibits the SDF-1alpha (CXCL12)-induced T cell migration through fibronectin (FN), and that this inhibition is mediated by the down-regulation of (i) the reorganization of cortical actin and the subsequent T cell polarization, and (ii) T cell adhesion to FN. Moreover, allicin also inhibited T cell adhesion to endothelial cells and transendothelial migration. The mechanisms underlying these inhibitory effects of allicin are associated with its ability to down-regulate the phosphorylation of Pyk2, an intracellular member of the focal adhesion kinases, and to reduce the expression of the VCAM-1- and FN-specific alpha4beta1-integrin (VLA-4). The ability of allicin to down-regulate these chemokine-induced and VLA-4-mediated T cell functions explains its beneficial biological effects in processes where T cells play an important role and suggests that allicin may be used therapeutically with chronic inflammatory diseases. 相似文献
2.
J M Carballido N Carballido-Perrig G Terres C H Heusser K Blaser 《European journal of immunology》1992,22(6):1357-1363
Protein antigens with both allergenic and immunoprotective properties represent appropriate molecules to study IgE and IgG regulation. We have established a panel of T cell clones specific to bee venom phospholipase A2 (PLA) from human individuals allergic, hyposensitized or immune (protected) to bee sting. All clones obtained were CD3+, CD4+ and expressed alpha, beta T cell receptor. Depending on the T cell clone, maximal stimulation required 1 to 100 micrograms/ml of PLA, and the addition of interleukin (IL)-2 and/or IL-4 increased their antigen-dependent proliferation. Following antigen stimulation, the clones produced IL-4, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor. Most clones also produced tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor beta (TNF-beta), and some produced IL-5 and/or IL-2. Both absolute and relative amounts of secreted cytokines depended on the antigen concentration. At low antigen doses, IL-4 was produced but little or not IFN-gamma, whereas at higher PLA concentrations significant amounts of both IL-4 and IFN-gamma were obtained. Thus, these PLA-specific T cell clones could be classified according to the changes in the ratio of IL-4/IFN-gamma production in response to increasing antigen concentrations. Clones derived from allergic and hyposensitized individuals required higher critical amounts of antigen for IFN-gamma induction, and expressed increasing IL-4/IFN-gamma ratios with increasing concentrations of PLA. Modulation of cytokine patterns by the dose of the antigen may be a driving force for IgE or IgG formation resulting in allergy or immunoprotection. 相似文献
3.
Ayelet Gonen Dror Harats Aharon Rabinkov Talia Miron David Mirelman Meir Wilchek Lev Weiner Esfir Ulman Hana Levkovitz Dikla Ben-Shushan Aviv Shaish 《Pathobiology》2005,72(6):325-334
OBJECTIVE: Garlic (Allium sativum) has been suggested to affect several cardiovascular risk factors. Its antiatherosclerotic properties are mainly attributed to allicin that is produced upon crushing of the garlic clove. Most previous studies used various garlic preparations in which allicin levels were not well defined. In the present study, we evaluated the effects of pure allicin on atherogenesis in experimental mouse models. METHODS AND RESULTS: Daily dietary supplement of allicin, 9 mg/kg body weight, reduced the atherosclerotic plaque area by 68.9 and 56.8% in apolipoprotein E-deficient and low-density lipoprotein (LDL) receptor knockout mice, respectively, as compared with control mice. LDL isolated from allicin-treated groups was more resistant to CuSO(4)-induced oxidation ex vivo than LDL isolated from control mice. Incubation of mouse plasma with (3)H-labeled allicin showed binding of allicin to lipoproteins. By using electron spin resonance, we demonstrated reduced Cu(2+) binding to LDL following allicin treatment. LDL treatment with allicin significantly inhibited both native LDL and oxidized LDL degradation by isolated mouse macrophages. CONCLUSIONS: By using a pure allicin preparation, we were able to show that allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages. 相似文献
4.
Defective functional response to membrane stimuli in lymphocytes from patients with benign prostatic hyperplasia. 下载免费PDF全文
M Prez-Blas B Martínez-Martín J Carballido J Hontoria L I Salazar C Olivier M Alvarez-Mon 《Clinical and experimental immunology》1995,101(3):521-526
Benign prostatic hyperplasia (BPH) is a local disturbance in the prostate that may involve an inflammatory infiltrate predominantly composed of activated lymphocytes and macrophages. The activation and proliferative response of T lymphocytes to different mitogenic signals has been analysed in peripheral blood mononuclear cells (PBMC) from 45 patients with BPH and 55 healthy controls. The PBMC obtained from the patients showed a significant specific impairment in proliferation, CD25 expression and IL-2 production in response to stimulation with lectins (phytohaemagglutinin (PHA), concanavalin A (Con A)), that was not corrected by the addition of IL-2 or of phorbol esters (phorbol myristate acetate (PMA)). Also, the CD28 response was defective in patient PBMC. Activation with anti-CD3 or anti-CD2 MoAbs was normal, but the addition of PMA to these stimuli provoked a significant defective response. Only the use of transmembrane stimuli (PMA and ionomycin) elicited responses similar to those found in the control group. The results indicate that peripheral T lymphocytes from BPH patients show a functional impairment that is mainly explained by an alteration of membrane signals (PHA, CD28) and is distal to protein kinase C (PKC) activation. 相似文献
5.
Allicin stimulates lymphocytes and elicits an antitumor effect: a possible role of p21ras 总被引:7,自引:0,他引:7
Patya M Zahalka MA Vanichkin A Rabinkov A Miron T Mirelman D Wilchek M Lander HM Novogrodsky A 《International immunology》2004,16(2):275-281
Allicin, the main organic allyl sulfur component in garlic, exhibits immune-stimulatory and antitumor properties. Allicin stimulated [(3)H]thymidine incorporation in mouse splenocytes and enhanced cell-mediated cytotoxicity in human peripheral mononuclear cells. Multiple administration (i.p.) of allicin elicited a marked antitumor effect in mice inoculated with B-16 melanoma and MCA-105 fibrosarcoma. The immune-stimulatory and antitumor effects of allicin are characterized by a bell-shaped curve, i.e. allicin at high, supra-optimal concentrations is less effective or inhibitory. Allicin induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in human peripheral mononuclear cells, and also in wild-type Jurkat T-cells. Allicin failed to activate ERK1/2 in Jurkat T cells that express p21(ras), in which Cys118 was replaced by Ser. These cells are not susceptible to redox-stress modification and activation. We postulate that the immune stimulatory effect of allicin is mediated by redox-sensitive signaling such as activation of p21(ras). It is suggested that the antitumor effect of allicin is related to its immune-stimulatory properties. 相似文献
6.
7.
M.-H. Lachapelle P. Miron R. Hemmings C. Baron D. C. Roy 《American journal of reproductive immunology (New York, N.Y. : 1989)》1996,35(1):5-13
Lachapelle M-H, Miron P, Hemmings R, Baron C, Roy DC. Flow-cytometric characterization of hematopoietic cells in non-pregnant human endometrium. Am J Reprod Immunol 1996; 35:5–13 cP Munksgaard, Copenhagen PROBLEM: Immunologic evaluation and quantitation of hematopoietic cells in human endometrium has been difficult to perform, particularly in nonpregnant subjects. In this study, we describe a method for the flow-cytometric characterization of hematopoietic cells present in the endometrium of non-pregnant women. METHOD: Endometrial biopsy samples from normal donors were first mechanically disrupted and filtered to generate a single-cell suspension of leukocyte-enriched endometrial cells. Cells were labeled with a panel of monoclonal antibodies, stained with propidium iodide (PI), and one- or two-color flow-cytometric analysis performed on cells excluding PI. RESULTS: The methodology described in this study was highly reproducible in experiments evaluating the interrun and intrarun variability. We then determined the immunophenotypic profile of endometrial leukocytes from 12 normal females. The majority of leukocytes were T cells (CD3: 47%; CD4: 24%; CD8: 28%) with an important contingent of NK cells (CD56: 32%), the majority of which harbored the unusual CD16-CD56 bright phenotype, and a minority of B cells (CD20: 6%) and monocytes (CD14: 7%). CONCLUSIONS: Flow cytometry can be used to assess antigen expression on the surface of endometrial leukocytes from nonpregnant women. In future studies, it will be possible to use this approach to investigate the role of immune cell populations in the endometrium of patient experiencing reproductive failure. 相似文献
8.
9.
Dae Won Kim Elaine Tan Jun-Min Zhou Michael J. Schell Maria Martinez James Yu Estrella Carballido Rutika Mehta Jonathan Strosberg Iman Imanirad Richard D. Kim 《British journal of cancer》2021,124(11):1803
Background MMR proficient (pMMR) colorectal cancer (CRC) is usually unresponsive to immunotherapy. Recent data suggest that ibrutinib may enhance the anti-tumour activity of anti-PD-1 immunotherapy. In this study, we evaluated the safety and efficacy of ibrutinib plus pembrolizumab in refractory metastatic CRC.Methods This was a phase 1/2 study in patients with refractory metastatic pMMR CRC. The primary endpoints for phases 1 and 2 were maximum tolerated dose (MTD) and disease control rate, respectively. The secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS).Results A total of 40 patients were enrolled. No dose-limiting toxicity was observed, and MTD was not identified. The highest tested dose of ibrutinib, 560 mg once daily, was combined with a fixed dose of pembrolizumab 200 mg every 3 weeks for the phase 2 portion. The most common grade 3/4 treatment-related adverse events were anaemia (21%), fatigue (8%) and elevated alkaline phosphatase (8%). Among 31 evaluable patients, 8 (26%) achieved stable disease, and no objective response was observed. The median PFS and OS were 1.4 and 6.6 months, respectively.Conclusion Ibrutinib 560 mg daily plus pembrolizumab 200 mg every 3 weeks appears to be well tolerated with limited anti-cancer activity in metastatic CRC.ClinicalTrials.gov identifier .Subject terms: NCT03332498Cancer immunotherapy, Colorectal cancer 相似文献
10.