全文获取类型
收费全文 | 17013篇 |
免费 | 2016篇 |
国内免费 | 638篇 |
专业分类
耳鼻咽喉 | 61篇 |
儿科学 | 457篇 |
妇产科学 | 128篇 |
基础医学 | 3892篇 |
口腔科学 | 274篇 |
临床医学 | 1389篇 |
内科学 | 3118篇 |
皮肤病学 | 353篇 |
神经病学 | 620篇 |
特种医学 | 242篇 |
外国民族医学 | 3篇 |
外科学 | 1287篇 |
综合类 | 2408篇 |
现状与发展 | 10篇 |
预防医学 | 1104篇 |
眼科学 | 242篇 |
药学 | 1372篇 |
9篇 | |
中国医学 | 1047篇 |
肿瘤学 | 1651篇 |
出版年
2024年 | 105篇 |
2023年 | 590篇 |
2022年 | 966篇 |
2021年 | 1293篇 |
2020年 | 961篇 |
2019年 | 782篇 |
2018年 | 672篇 |
2017年 | 795篇 |
2016年 | 793篇 |
2015年 | 706篇 |
2014年 | 899篇 |
2013年 | 1252篇 |
2012年 | 797篇 |
2011年 | 783篇 |
2010年 | 698篇 |
2009年 | 618篇 |
2008年 | 579篇 |
2007年 | 612篇 |
2006年 | 598篇 |
2005年 | 524篇 |
2004年 | 448篇 |
2003年 | 401篇 |
2002年 | 404篇 |
2001年 | 396篇 |
2000年 | 296篇 |
1999年 | 258篇 |
1998年 | 243篇 |
1997年 | 209篇 |
1996年 | 191篇 |
1995年 | 181篇 |
1994年 | 172篇 |
1993年 | 135篇 |
1992年 | 127篇 |
1991年 | 151篇 |
1990年 | 96篇 |
1989年 | 85篇 |
1988年 | 93篇 |
1987年 | 115篇 |
1986年 | 89篇 |
1985年 | 105篇 |
1984年 | 109篇 |
1983年 | 66篇 |
1982年 | 93篇 |
1981年 | 47篇 |
1980年 | 36篇 |
1979年 | 32篇 |
1978年 | 15篇 |
1977年 | 17篇 |
1976年 | 16篇 |
1973年 | 7篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Valledor AF 《Immunobiology》2005,210(2-4):127-132
Macrophages play essential roles in infection and resolution of inflammation. This review summarizes recent findings that suggest a relevant role for the nuclear receptor liver X receptor (LXR) in the evolution of immune responses. By exerting both positive and negative regulation of specific macrophage gene expression networks, LXRs display anti-inflammatory activities and promote macrophage survival in bacterial infection settings. Agonists that activate the LXR pathway may be used to enhance innate immunity to highly virulent pathogens that otherwise induce macrophage apoptosis as a means to subvert host immune defense. 相似文献
72.
73.
The effect of surface sugars of liposomes on the immunological responses to entrapped antigen has been investigated. alpha-Mannose and beta-galactose were grafted on the surface of liposomes containing lysozyme by covalent coupling of p-aminophenyl-D-glycosides to phosphatidyl ethanolamine liposomes using glutaraldehyde. Subcutaneous administration of antigen entrapped in beta-galactose liposomes stimulated an antibody response comparable to that elicited by sugar-free neutral liposomes. However, alpha-mannose bearing liposomes with entrapped lysozyme elicited an immune response similar to that induced by lysozyme in saline. Based on these observations it is suggested that alpha-mannose liposomes, that are specifically recognized by macrophages, are taken up rapidly by receptor mediated endocytosis and that the entrapped antigen is then rapidly degraded, resulting in low antibody production. 相似文献
74.
Differences in cytokine secretion by intestinal mononuclear cells, peripheral blood monocytes and alveolar macrophages from HIV-infected patients. 总被引:2,自引:1,他引:2 下载免费PDF全文
M Steffen H C Reinecker J Petersen C Doehn I Pflüger A Voss A Raedler 《Clinical and experimental immunology》1993,91(1):30-36
Mononuclear cells of the lamina propria (LpMNC), isolated from endoscopically taken biopsies of the large bowel from AIDS patients, were analysed for their ability to secrete tumour necrosis factor-alpha (TNF-alpha), IL-1 beta and IL-6. Stimulation of LpMNC from normal controls with pokeweed mitogen (PWM) led to a time- and dose-dependent enhancement of TNF-alpha, IL-1 beta and IL-6 secretion. In contrast, PWM stimulation of LpMNC from AIDS patients resulted in only a small increase in TNF-alpha release. Constitutive secretion of IL-1 beta and IL-6 in these patients was already increased to the concentration range of stimulated cells from normal controls and could not be further increased, probably due to maximal in vivo stimulation. Secretion of TNF-alpha, IL-1 beta and IL-6 by peripheral blood monocytes (PBM) and alveolar macrophages from AIDS patients was elevated with or without stimulation compared with normal controls. Obviously, the regulation of TNF-alpha secretion is dependent on the microenvironment. Since it is known that interferon-gamma (IFN-gamma) may induce the production of TNF-alpha, the secretion of this cytokine was examined. Release of IFN-gamma was constitutively and under stimulation lowered in LpMNC from AIDS patients compared with normal controls. Addition of IFN-gamma to LpMNC did not result in enhanced TNF-alpha secretion. Our data indicate a defective function of intestinal mononuclear cells in AIDS patients as shown by the diminished TNF-alpha secretion. 相似文献
75.
钟向真 《中国优生与遗传杂志》2006,14(11):70-71,74
目的探讨三种不同方法治疗自身免疫型习惯性流产的临床效果。方法选取78例确诊为自身免疫异常引起的习惯性流产患者,分为4组,1为阿司匹林+泼尼松组(22例),2为阿司匹林+肝素组(18例),3为静丙组(20例),4为对照组(18例),不接受任何治疗,用卡方检验比较各组妊娠成功率。结果1、2、3组与对照组分别比较,差异均有统计学意义(P〈0.05),但3种治疗方法之间无显著差异(P〉0.05);1组出现了胎膜早破、妊娠期高血压疾病等妊娠合并症,2组出现了早产和消化道出血,但各组发生率无统计学差异(P〉0.05)。结论传统的激素、抗凝剂和被动免疫疗法均有一定疗效,但三者之间疗效无差异。 相似文献
76.
Toxoplasma gondii is able to invade phagocytic cells of the monocyte-macrophage lineage and replicates within a parasitophorous vacuole. Since macrophages may activate specific T lymphocytes by presenting pathogen-derived antigens in association with molecules of the MHC, we investigated the in vitro expression of host cell molecules involved in antigen processing and presentation before and during infection of murine bone marrow-derived macrophages (BMM) with T. gondii. Fifty-one hours after addition of T. gondii tachyzoites at different parasite-to-host ratios, up-regulation of total MHC class II molecules by interferon-gamma (IFN-γ) was dose-dependently abrogated in up to 50% of macrophages compared with uninfected control cultures. Quantitative analyses by flow cytometry revealed that the IFN-γ-induced surface expression of class II antigens as well as the IFN-γ-induced up-regulation of class I molecules was significantly decreased in T. gondii-infected macrophage cultures compared with uninfected controls. However, the constitutive expression of MHC class I antigens was not altered after parasitic infection, and infected BMM remained clearly positive for these molecules. After infection of macrophages preactivated with IFN-γ for 48 h, T. gondii also actively down-regulated an already established expression of MHC class II molecules. Furthermore, kinetic analysis revealed that the reduction in intracellular and plasma membrane-bound class II molecules started ≈ 20 h after infection. While MHC class II antigens were most prominently reduced in parasite-positive host cells, culture supernatant from T. gondii-infected BMM cultures also significantly inhibited expression of these molecules in uninfected macrophages. However, down-regulation of MHC class II molecules was not mediated by an increased production of prostaglandin E2, IL-10, transforming growth factor-beta or nitric oxide by infected BMM compared with uninfected controls. Our data indicate that intracellular T. gondii interferes with the MHC class I and class II antigen presentation pathway of murine macrophages and this may be an important strategy for evasion from the host's immune response and for intracellular survival of the parasite. 相似文献
77.
Gaëlle Dzangué-Tchoupou Kuberaka Mariampillai Loïs Bolko Damien Amelin Wladimir Mauhin Aurélien Corneau Catherine Blanc Yves Allenbach Olivier Benveniste 《Autoimmunity reviews》2019,18(4):325-333
Background
Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.Objectives
Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers.Methods
Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients).Results
Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97.Conclusion
Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease. 相似文献78.
Bonnet F Savès M Morlat PH Droz C Chêne G Peuchant E Bernard N Lacoste D Salamon R Beylot J 《Journal of clinical immunology》2002,22(2):75-82
We assessed the correlations between some plasma markers of immune activation (soluble receptors of interleukin 2 (sIL2-R) and TNFp75 (sTNFII-R) and usual markers of HIV infection in patients treated with protease-inhibitors (PI). Forty-six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort from the initiation of a PI-containing regimen (M0). Measurements of CD4+cell count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The evolution of sIL2-R from baseline to M12 was significantly different between immunological responders (IR) (CD4+count above 200/mm3 for subject having less than 200 CD4 +/mm3 at inclusion, or increase of at least 50 CD4+/mm3 for others) (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0 and M12 was significantly different between virological responders (VR) (plasma HIV-1 RNA less than 500 copies/ml at M12) (–2.5 ng/ml) and non-VR (+0.2 ng/ml) (P =0.02). Our study shows significative correlations between the evolutions of soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV-RNA responses in patients under HAART. 相似文献
79.
Depressed lymphocyte transformation and the role of prostaglandins in atopic dermatitis. 总被引:2,自引:1,他引:2 下载免费PDF全文
T Jakob B N Huspith Y E Latchman R Rycroft J Brostoff 《Clinical and experimental immunology》1990,79(3):380-384
We have shown that peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis have a reduced in vitro proliferative responsiveness to concanavalin A when compared with non-atopic controls. Addition of the cyclo-oxygenase inhibitor indomethacin caused a significant enhancement of the mitogen response in the patients, indicating a suppressive effect of cyclooxygenase products. We have further demonstrated increased levels of prostaglandin E2 in the supernatants of the PBMC cultures and increased levels of IgE immune complexes in the sera of the atopic dermatitis patients and therefore hypothesize that IgE immune complexes may cause increased monocyte production of prostaglandins which in turn appears to be responsible for a reduced lymphocyte proliferation. 相似文献
80.
Circulating immune complexes may play a regulatory and pathogenic role in experimental autoimmune uveoretinitis. 总被引:1,自引:0,他引:1 下载免费PDF全文
E Kasp M R Stanford E Brown A G Coombes D C Dumonde 《Clinical and experimental immunology》1992,88(2):307-312
We compared the time course of changes in serum levels of circulating immune complexes (CICs) and of IgG antibody after sensitization of albino Lewis and pigmented Lister strain rats with uveitogenic (retinal S-antigen) and non-uveitogenic (ovalbumin) protein antigens of comparable molecular weight. Normal levels of CICs were far lower in Lewis rats in which experimental autoimmune uveoretinitis (EAU) takes the form of a severe panuveitis, than in Lister rats, in which the disease is mild, focal, confined to the posterior segment, and of lower incidence. After sensitization with either S-antigen or ovalbumin, polyethylene-glycol-precipitable CIC (PEG-CIC) peaked and fell as IgG antibody levels rose in both rat strains. However, peak levels of PEG-CIC were lower and subsequent IgG antibody levels were higher in the Lewis strain than in the less susceptible Lister strain. In both strains of rat these linked PEG-CIC/IgG antibody responses occurred earlier after sensitization with uveitogenic (S-) antigen than with ovalbumin, whether or not individual S-antigen-sensitized Lister rats developed EAU. In contrast, complement-binding CIC rose substantially only in those rats of both strains displaying EAU in response to S-antigen and not in response to ovalbumin. We suggest that immune complex (idiotypic) regulation of IgG antibody responses may be more readily perturbed by a pathogenic autoantigen (S-antigen) than by a bland antigen (ovalbumin). We also suggest that differences between the balance of regulatory and pathogenic CIC responses to uveitogenic retinal antigen may underlie or reflect strain differences in susceptibility to and severity of EAU. 相似文献