全文获取类型
收费全文 | 375篇 |
免费 | 119篇 |
国内免费 | 8篇 |
专业分类
儿科学 | 18篇 |
妇产科学 | 5篇 |
基础医学 | 224篇 |
口腔科学 | 6篇 |
临床医学 | 19篇 |
内科学 | 74篇 |
皮肤病学 | 9篇 |
神经病学 | 15篇 |
特种医学 | 1篇 |
外科学 | 13篇 |
综合类 | 40篇 |
预防医学 | 18篇 |
眼科学 | 8篇 |
药学 | 36篇 |
中国医学 | 8篇 |
肿瘤学 | 8篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 10篇 |
2020年 | 11篇 |
2019年 | 8篇 |
2018年 | 6篇 |
2017年 | 9篇 |
2016年 | 6篇 |
2015年 | 4篇 |
2014年 | 26篇 |
2013年 | 20篇 |
2012年 | 16篇 |
2011年 | 23篇 |
2010年 | 8篇 |
2009年 | 16篇 |
2008年 | 13篇 |
2007年 | 22篇 |
2006年 | 13篇 |
2005年 | 6篇 |
2004年 | 11篇 |
2003年 | 11篇 |
2002年 | 6篇 |
2001年 | 3篇 |
2000年 | 10篇 |
1999年 | 23篇 |
1998年 | 33篇 |
1997年 | 28篇 |
1996年 | 20篇 |
1995年 | 22篇 |
1994年 | 23篇 |
1993年 | 22篇 |
1992年 | 14篇 |
1991年 | 13篇 |
1990年 | 21篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
排序方式: 共有502条查询结果,搜索用时 15 毫秒
41.
冠心病与IL-10,IL-4和IFN-γ浓度关系的研究 总被引:2,自引:0,他引:2
目的研究冠心病患者血清白细胞介素-10(IL-10)、白细胞介素-4(IL-4)、γ干扰素(IFN-γ)浓度变化及其对冠心病发病的影响。方法选取非冠心病组28人,按相同性别、年龄配对原则,通过冠脉造影选取冠心病患者28人。用放射免疫法检测两组血清IL-10t和IL-4浓度;酶联免疫吸附法检测两组血清IFN-γ浓度。结果两组IL-10浓度差异无统计学意义(P>0.05);冠心病组较对照组IL-4浓度增高(P<0.05);冠心病组较对照组IFN-γ浓度明显增高(P<0.01);Logistic回归显示IL-4及IFN-γ对冠心病发病的影响有统计学意义(均为P<0.05)。结论内源性IL-10不足以阻止冠心病的发生、发展;IFN-γ和IL-4促进冠心病的发生、发展。 相似文献
42.
The inhibitory mechanism of interferon-gamma (IFN-γ) on the fibroblasts from Tenon‘s capsule was studied. By using immunohistochemical SP method and pathological image system, the inhibitory effects of IFN-γ on the expression of transforming growth factor beta receptor I in the in vitro cultured fibroblasts from Tenon‘s capsule were quantitatively analyzed. The results showed that IFN-γ could reduce the expression of transforming growth factor beta receptor I in the fibroblasts with the following dose-effect relationship: Y= 1937.5—134.2 Igx (r=- 0. 971, P<0.01).It was concluded that IFN-γ could inhibit the expression of transforming growth factor beta receptor I in the fibroblasts from Tenon‘s capsule. The modulation of the transforming growth factor beta receptor I expression by IFN-γ, may be beneficial to the alleviation of the hyperplasia of scar after trabeculectomy. 相似文献
43.
44.
Xiao ZY Zheng QY Jiang YY Zhou B Yin M Wang HB Zhang JP 《Acta pharmacologica Sinica》2004,25(6):817-821
AIM: To investigate the influence of esculentoside A (EsA) on immunological function and its mechanism of antiinflammation. METHODS: Interleukin-1 production was measured by thymocyte co-stimulating assay; the radioactivity of [^3H]arachidonic acid (AA) was used to evaluate the release of AA; prostaglandin E2 production was measured with radioimmunoassay (RIA); IL-2 and IFN-γ were detected by ELISA method. RESULTS: EsA (3-12μmol/L)could potently inhibit the production of IL-1 and PGE2 from both silent and LPS induced macrophages.EsA had no significant effect on the release of AA from murine macrophages. EsA could inhibit the production of IL-2 from murine lymphocytes induced by ConA, but not affect the production from silent lymphocytes. EsA showed no effect on the production of IFN-γ from both silent and ConA induced lymphocytes. CONCLUSION:EsA could affect the immunological function through inhibiting the production of IL-2 from activated splenocytes and the inhibition of production of IL- 1 and PGE2 might be one of the anti-inflammation mechanisms of EsA. 相似文献
45.
Jin H Vicario PP Zweerink H Goyal S Hanlon WA Dorn CP Mills SG DeMartino JA Cascieri MA Struthers M 《Biochemical pharmacology》2003,66(2):321-330
Species selectivity of chemokine receptor antagonists is a potential deterrent to making preclinical assessments in vivo. To determine if rhesus monkey disease models could support these assessments, we pharmacologically and functionally characterized recombinant rhesus CCR2B receptor. For these studies we obtained the CCR2B coding region by PCR from genomic rhesus DNA and expressed the receptor as stable transfectants in Chinese Hamster Ovary cells. The surface expression of recombinant rhesus CCR2B was detected by flow cytometry using a commercially available monoclonal anti-hCCR2B antibody. This antibody was used to detect rhCCR2B on monocytes in peripheral blood mononuclear cell preparations from rhesus whole blood. The recombinantly expressed CCR2B exhibited similar high affinity binding to the CCR2 chemokine ligands from rhesus and human 125I-rhMCP-1 (K(d)=433+/-14 pM) and 125I-hMCP-1 (K(d)=550+/-256 pM). In competition binding, the receptor exhibited selective high affinity binding to the monocyte chemoattractant protein (MCP) family chemokines with little affinity for most other members of the CC family of chemokines. One exception was eotaxin, a high affinity ligand for CCR3, which bound to rhesus CCR2B receptor (K(i)=1467+/-205 pM). Chemokines which exhibited binding affinity for the receptor were tested for their ability to induce intracellular calcium release. In these experiments the relative potencies of the MCP family of chemokines for rhCCR2B were similar to the observed binding affinities. In contrast, eotaxin was functionally inactive as an antagonist or agonist to this receptor. TAK-799 (N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium chloride), a dual CCR2/CCR5 antagonist, demonstrated high affinity for the rhesus CCR2B in competition with 125I-hMCP-1 binding to the receptor (K(i)=0.5 nM) and also potently blocked the MCP-1 induced calcium mobilization mediated through the receptor. 相似文献
46.
Kuttler B Steveling A Klöting N Morgenstern O Wanka H 《Biochemical pharmacology》2003,66(12):2437-2448
Autoimmune beta-cell destruction occurs directly by cell-mediated cytotoxicity or indirectly by cytokines released from infiltrating lymphocytes. Cytokines (IL-1beta/IFN-gamma) modify or induce expression of MHC antigens and ICAM-1 on beta-cells which can lead to an improved binding of T-lymphocytes to beta-cells and finally to an enhanced cell-mediated cytotoxicity. Cytokines also induce Fas-expression and inducible nitric oxide synthase (iNOS) causing generation of nitric oxide (NO) which is toxic for beta-cells. The iNOS inhibitor aminoguanidine (AG) delays diabetes onset, but does not reduce diabetes incidence. We wanted to know whether AG inhibits cytokine-induced expression of Fas, MHC antigens and ICAM-1 on beta-cells of LEW.1W and BB/OK rat islets after culture with IL-1beta/IFN-gamma. NO was completely inhibited by 5.0 mmol/L AG while 0.5 mmol/L had no inhibitory effect. AG downregulated Fas-expression on the surface of beta-cells. Cytokine-induced/enhanced expression of MHC class-II and ICAM-1 was not affected by any AG concentration. AG syngergistically increased cytokine-induced enhancement of MHC class-I antigen density. AG possibly blocks the indirect pathway of beta-cell damage in vivo due to inhibition of Fas and iNOS and improves direct cell-mediated cytotoxicity due to drastic increased MHC class-I expression. Inhibition of only one pathway of beta-cell destruction is not sufficient to prevent diabetes. 相似文献
47.
Immunomodulatory activity of resveratrol: discrepant in vitro and in vivo immunological effects 总被引:9,自引:0,他引:9
Gao X Deeb D Media J Divine G Jiang H Chapman RA Gautam SC 《Biochemical pharmacology》2003,66(12):2427-2435
trans-Resveratrol is a dietary polyphenolic compound present in grapes, which has been shown to exhibit strong anti-inflammatory, antioxidant, and chemopreventive activities. In this study we have compared the in vitro and in vivo effects of resveratrol on the development of various cell-mediated immune responses, including mitogen/antigen-induced T cell proliferation, induction of cytotoxic T lymphocytes (CTLs), interleukin-2 (IL-2) induced lymphokine activated killer cells, and cytokine production. We found significant suppression (>90%) of the mitogen/antigen-induced T cell proliferation and development of allo-antigen specific CTLs in vitro with resveratrol at a concentration of 25 microM. Intragastric administration of resveratrol (2 mg daily) to mice for 4 weeks showed no effect on age-related gain in body weight, peripheral blood cell counts (WBC, RBC, or platelets), or the cellularity of bone marrow or spleen. The CD4(+) and CD8(+) T cells in spleen or colony-forming units-total in the marrow also remained unaffected by treatment with resveratrol. Spleen cells, which were stimulated in vitro after being removed from mice which had been administered resveratrol for 2 or 4 weeks, showed no significant change in IL-2 or concanavalin A induced proliferation of T cells or production of IL-2 induced lymphokine activated killer cells. Further, the production of in interferon-gamma and IL-12 was not affected by administration of resveratrol, but production of tumor necrosis factor-alpha was reduced. Even when conducted entirely in vivo, treatment with resveratrol was found to only marginally reduce allo-antigen induced T cell proliferation and the generation of CTLs in the draining lymph nodes. Thus, even though resveratrol strongly inhibits T cell proliferation and production of cytolytic cells in vitro, oral administration of resveratrol for 4 weeks does not induce hematologic or hematopoietic toxicity, and only marginally reduces the T cell-mediated immune responses. 相似文献
48.
目的:观察放射治疗对BALB/c小鼠肾癌的抑瘤作用.方法:采用Annexin-Ⅴ-FITC/PI法检测不同剂量放疗后Renca细胞的凋亡率,建立BALB/c小鼠的肾癌细胞移植瘤放射治疗的模型.采用ELISA试剂盒检测小鼠脾淋巴细胞的细胞因子IL-2、IFN-γ分泌水平.结果:①在一定照射剂量范围内,Renca细胞的凋亡率随剂量的增加而升高.②放疗组小鼠移植瘤生长速度较对照组明显减慢.③放疗组小鼠脾细胞分泌IL-2及IFN-γ明显较肿瘤对照组升高.结论:放疗组小鼠肿瘤生长受到明显抑制,与放疗引发的Renca细胞凋亡和小鼠脾细胞分泌IL-2及IFN-γ能力增强有关. 相似文献
49.
Simultaneous detection of IFN-gamma and IL-4 in lesional tissues and whole unstimulated saliva from patients with oral lichen planus 总被引:1,自引:0,他引:1
Xiao-an Tao Chun-yang Li Nelson L. Rhodus Juan Xia Xiao-ping Yang Bin Cheng 《Journal of oral pathology & medicine》2008,37(2):83-87
Background: Although the roles of interferon (IFN)-gamma and interlekin (IL)-4 in oral lichen planus (OLP) have been described extensively in past decades, the available results are controversial. Moreover, few studies have utilized simultaneous detection of cytokines in local tissues and saliva to determine whether salivary cytokines could reflect the fact of local lesions.
Methods: IFN-gamma and IL-4 were determined simultaneously in lesions and whole unstimulated saliva (WUS) from OLP patients with various clinical forms.
Results: In OLP lesions, both IFN-gamma and IL-4 in erythematous/ulcerated OLP were higher significantly than that in control specimens. In WUS, however, only IFN-gamma of erythematous/ulcerated OLP was increased compared with control. Remarkably, IFN-gamma and IL-4 in WUS showed a more significant correlation to those in local tissues of all subjects.
Conclusion: These results indicate that both IFN-gamma and IL-4 may play more important role in pathogenesis of erythematous/ulcerated OLP, and changes of these proinflammatory cytokines in WUS may reflect the status of the OLP lesion. 相似文献
Methods: IFN-gamma and IL-4 were determined simultaneously in lesions and whole unstimulated saliva (WUS) from OLP patients with various clinical forms.
Results: In OLP lesions, both IFN-gamma and IL-4 in erythematous/ulcerated OLP were higher significantly than that in control specimens. In WUS, however, only IFN-gamma of erythematous/ulcerated OLP was increased compared with control. Remarkably, IFN-gamma and IL-4 in WUS showed a more significant correlation to those in local tissues of all subjects.
Conclusion: These results indicate that both IFN-gamma and IL-4 may play more important role in pathogenesis of erythematous/ulcerated OLP, and changes of these proinflammatory cytokines in WUS may reflect the status of the OLP lesion. 相似文献
50.
Cytokine-producing cells in peripheral blood of children with coeliac disease secrete cytokines with a type 1 profile.
下载免费PDF全文
![点击此处可从《Clinical and experimental immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Coeliac disease (CoD) is a small intestinal disorder characterized by crypt cell hyperplasia and villous atrophy, and the production of cytokines from T cells and macrophages are of importance for the histological changes seen in CoD. A peroral immunization with an antigen, which gives rise to a mucosal immune response, may increase the levels of circulating cytokine-producing cells, and we wanted to obtain a better picture of an eventual emergence of activated circulating T cells in the peripheral blood in children with CoD. The cytokine expression of interferon-gamma (IFN-gamma), IL-4, IL-6 and IL-10 was measured at the single-cell level by an ELISPOT method in 38 children with CoD. The numbers of IFN-gamma-producing cells in the peripheral blood was increased in children with untreated CoD (P < 0.01) and after gluten challenge (P < 0.05) compared with healthy controls. Also, the numbers of IL-6-producing cells were increased (P < 0.05) after gluten challenge compared with the healthy controls. A paired comparison showed that the numbers of IFN-gamma-producing cells increased after gluten challenge (P < 0.05), whereas no such change was seen for IL-4- or IL-10-producing cells. There were no differences in the numbers of IFN-gamma-producing cells between the group of children with treated CoD and the groups of untreated or challenged CoD children. IL-4 production correlated with serum levels of total IgE. These results show that circulating mononuclear cells in children with active CoD secrete cytokines compatible with a type 1 response. 相似文献