全文获取类型
收费全文 | 15653篇 |
免费 | 1082篇 |
国内免费 | 397篇 |
专业分类
耳鼻咽喉 | 84篇 |
儿科学 | 322篇 |
妇产科学 | 238篇 |
基础医学 | 3250篇 |
口腔科学 | 253篇 |
临床医学 | 920篇 |
内科学 | 2437篇 |
皮肤病学 | 358篇 |
神经病学 | 949篇 |
特种医学 | 243篇 |
外科学 | 2088篇 |
综合类 | 1683篇 |
现状与发展 | 1篇 |
预防医学 | 1013篇 |
眼科学 | 162篇 |
药学 | 1756篇 |
3篇 | |
中国医学 | 437篇 |
肿瘤学 | 935篇 |
出版年
2023年 | 194篇 |
2022年 | 320篇 |
2021年 | 476篇 |
2020年 | 401篇 |
2019年 | 673篇 |
2018年 | 546篇 |
2017年 | 497篇 |
2016年 | 449篇 |
2015年 | 512篇 |
2014年 | 869篇 |
2013年 | 917篇 |
2012年 | 742篇 |
2011年 | 1019篇 |
2010年 | 799篇 |
2009年 | 832篇 |
2008年 | 696篇 |
2007年 | 794篇 |
2006年 | 771篇 |
2005年 | 687篇 |
2004年 | 627篇 |
2003年 | 534篇 |
2002年 | 362篇 |
2001年 | 265篇 |
2000年 | 243篇 |
1999年 | 201篇 |
1998年 | 159篇 |
1997年 | 136篇 |
1996年 | 142篇 |
1995年 | 133篇 |
1994年 | 115篇 |
1993年 | 90篇 |
1992年 | 75篇 |
1991年 | 75篇 |
1990年 | 57篇 |
1989年 | 48篇 |
1988年 | 49篇 |
1987年 | 49篇 |
1986年 | 49篇 |
1985年 | 148篇 |
1984年 | 194篇 |
1983年 | 151篇 |
1982年 | 193篇 |
1981年 | 160篇 |
1980年 | 130篇 |
1979年 | 142篇 |
1978年 | 84篇 |
1977年 | 73篇 |
1976年 | 61篇 |
1975年 | 64篇 |
1973年 | 47篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
91.
目的:确定SLE模型小鼠IL-10RA基因变异及其与SLE表现型是否存在关联。方法:用微卫星遗传标记及数量性状位点(QTL)分析方法确定SLE模型小鼠B/W F1的SLE易感基因精确染色体定位并选取候选易感基因,对候选易感基因进行测序分析,选取有基因序列异常的候选易感基因进行PCR-SSCP分析,确定候选易感基因碱基序列变异位点与抗染色质抗体、抗DNA抗体,抗组蛋白抗体及蛋白尿等SLE表现型的相关关系。结果:QTL分析结果表明B/W F1×NZB小鼠抗染色质抗体易感基因与NZW型IL-10RA基因紧密连锁;测序分析发现IL-10RA基因编码区有18处碱基变异,其中7处碱基变异将导致编码氨基酸的变异;抗染色质抗体、抗DNA抗体,抗组蛋白抗体及蛋白尿等SLE表现型与NZW型IL-10RA基因密切相关。另一种SLE模型小鼠MRL的IL-10RA基因存在相同变异。结论:NZW小鼠IL-10RA基因编码区碱基序列存在变异,B/W F1×NZB小鼠SLE表现型与NZW小鼠第9染色体IL-10RA编码区碱基变异相关,提示IL-10RA可能是SLE模型小鼠的一个SLE易感基因。 相似文献
92.
Youssef AR Shen CR Lin CL Barker RN Elson CJ 《Clinical and experimental immunology》2005,139(1):84-89
New Zealand Black (NZB) mice spontaneously develop autoimmune haemolytic anaemia (AIHA). Here the effect of injecting NZB mice with plasmids encoding IL-4 (pIL-4) or IL-10 (pIL-10) on NZB disease was tested. Both constructs delayed the development of anaemia as judged by increased haematocrit values as compared with controls, but neither altered the IgG1 to IgG2 red blood cell (RBC) bound autoantibody levels. The increased haematocrit value was associated temporally with increased RBC bound IgG in NZB mice treated with pIL-10, but not pIL-4. By contrast, up-regulation of splenic macrophage FcgammaRIIb2 mRNA was associated temporally with increased haematocrit values in NZB mice given pIL-4. However, no such increase occurred in NZB mice that inhaled a peptide containing a dominant T-cell epitope, although this treatment is known to bias the autoimmune response towards Th2 and to reduce the severity of anaemia. It is considered that IL-4 treatment, in part, ameliorates NZB anaemia by increasing the expression of the inhibitory FcgammaRIIb2 and thereby reducing the capacity of splenic macrophages to phagocytose autoantibody coated RBC, but that this mechanism does not explain the beneficial effects of the inhaled peptide. 相似文献
93.
I. Urban D. de Wied 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1976,24(3):325-334
Summary The present experiments tested the sensitivity of theta activity to ACTH 4–10 a peptide known to facilitate the maintenance of conditioned behaviors. Hippocampal theta activity was induced by electrical stimulation of the reticular formation in freely moving rats. The administration of ACTH 4–10 produced a typical 0.5 c/s shift in dominant frequency and an increase in 7.5–9.0 c/s components of induced theta activity. The effects were maximal between 60–120 min after subcutaneous injection and lasted several hours. The fact, that a similar effect could be obtained by an increase in stimulus intensity suggests an elevated excitability in the theta generating system in the presence of the peptide. The possible significance of this finding for the maintenance of learned behavior is discussed. 相似文献
94.
S M BROOKES S B A COHEN E J PRICE L M C WEBB M FELDMANN R N MAINI P J W VENABLES 《Clinical and experimental immunology》1996,103(2):268-272
Sjögren''s syndrome (SS) is characterized by a focal periductal salivary gland infiltrate consisting mainly of T and B lymphocytes. Most of the T cells bear the memory of CD4+ Th-1-like phenotype and express high levels of class II, though CD8+ cells are also present. We have studied 17 labial salivary gland and 15 peripheral blood T cell clones from a patient with primary SS. The tissue clones were 71% CD8+ and 29% CD4+, and the peripheral blood-derived clones were 60% CD8+ and 40% CD4+. The CD4+ T cell clones from both the salivary gland and autologous peripheral blood were of the Th1 phenotype, in that they produced interferon-gamma (IFN-γ) and IL-2 but very little IL-4 after 24 h stimulation with phorbol myristate acetate and anti-CD3 antibody. The salivary gland-derived CD4+ clones produced 15 times more IL-10 (7·92 ng/ml) than peripheral blood-derived CD4+ clones (0·52 ng/ml, P≤0·02). The tissue CD8+ clones produced 1·2 times (P<0·04) more IFN-γ and CD4+ clones produced 3·5 times less IL-2 (P<0·02) than the respective PBM-derived clones. The accumulation of Th1-type cells producing high levels of IL-10 in the salivary gland suggests a specific immunoregulatory function at the site of inflammation in SS. 相似文献
95.
96.
Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival 总被引:14,自引:0,他引:14
Zhang M Wang Q Liu Y Sun Y Ding G Fu Z Min Z Zhu Y Cao X 《Journal of molecular medicine (Berlin, Germany)》2004,82(4):240-249
Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise, we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.Abbreviations
APC
Antigen-presenting cells
-
CTL
Cytotoxic T lymphocytes
-
DC
Dendritic cells
-
DC-IL-10
IL-10 gene-modified immature dendritic cells
-
iDC
Immature dendritic cells
-
IL-10
Interleukin-10
-
MLR
Mixed leukocyte reaction
-
MOI
Multiplicity of infection 相似文献
97.
Ping Xu Shuichi Hashimoto Hiroyuki Miyazaki Koushi Asabe Sachiko Shiraishi K. Sueishi 《Virchows Archiv : an international journal of pathology》1998,432(1):17-25
Morphometric analyses of the immunohistochemical expression of the Clara cell secretory 10-kDa protein (CC10) and surfactant
apoproteins A and B (SP-A and -B) were carried out on the developing bronchi and bronchioles of human fetuses and neonates.
We analysed the ratio of the number of CC10-positive cells per subepithelial length of the bronchial or bronchiolar basement
membrane and found that both the bronchial and the bronchiolar population of CC10-positive cells was significantly higher
than that of either SP-A or SP-B. In addition, CC10 was found to be distributed mainly in the bronchiole. CC10-positive cells
began to be recognized in the late pseudoglandular phase (15 weeks of gestation) and thereafter gradually increased in the
canalicular and terminal sac phases, which correspond to the active development period of the acini or peripheral airways.
The earliest expression of SP-A was also noted at 15 weeks of gestation, but its positive epithelial cells were present mainly
in the larger bronchi. Double immunohistochemical staining for CC10 and SP-A revealed that the CC10-positive cells lining
both the bronchi and bronchioles were different from the SP-A-positive cells. This finding suggests that CC10-positive cells
are functionally and developmentally heterogeneous in both fetal and neonatal lungs in humans
Received: 22 May 1997 / Accepted: 21 July 1997 相似文献
98.
A synthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis
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)
S. RAGNO V. R. WINROW P. MASCAGNI P. LUCIETTO F DI PIERRO C. J. MORRIS D. R. BLAKE 《Clinical and experimental immunology》1996,103(3):384-390
The heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10±7kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp 10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroES is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co-chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant-induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES nor the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N-terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased litres to both hsp10 and hsp65: hsp10-treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co-chaperonin in pathophysiological situations. 相似文献
99.
Profiles of ICAM-1 expression on cultured murine peritoneal macrophages infected with Mycobacterium avium complex (MAC) were examined, with special reference to modulating roles of TNF-alpha, TGF-beta, and IL-10. When macrophages were infected with MAC, ICAM-1 expression, measured by microscopic counting of ICAM-1+ macrophages stained with anti-ICAM-1 antibody, ELISA, and flow cytometric analysis, was rapidly increased, peaking at day 3 (early-phase up-regulation) due to endogenous TNF-alpha, and thereafter gradually declined to the normal level within 1 week or more (late-phase down-regulation). The late-phase ICAM-1 down-regulation was also seen in macrophages phagocytosing heat-killed MAC and those stimulated with lipopolysaccharide but not in macrophages phagocytosing latex beads. ICAM-1 mRNA expression was augmented markedly at day 1 after MAC infection and thereafter decreased. While TNF-alpha and IL-10 production by MAC-infected macrophages was observed during the first 3 days, TGF-beta production was initiated from day 3 and continued until day 14. Exogenously added TGF-beta strongly inhibited the early-phase increase in ICAM-1 expression by infected macrophages, and the blockade of endogenous TGF-beta with anti-TGF-beta antibody markedly inhibited late-phase ICAM-1 down-regulation. Moderate blocking effect was also observed for anti-IL-10 antibody. On the other hand, late-phase ICAM-1 down-regulation was not prevented by the addition of exogenous TNF-alpha. Therefore, TGF-beta and IL-10, especially the former, appear to play active roles in the late-phase down-regulation of ICAM-1 in MAC-infected macrophages during long-term cultivation. 相似文献
100.
Florence P. Haseltine Vincent A. Lynch Daniel L. Van Dyke W. Roy Breg Uta Francke John M. Opitz 《American journal of medical genetics. Part A》1982,13(2):115-123
Cells from three patients with early gonadal failure and a balanced reciprocal translocation involving the long arm of the X chromosome and an autosome were studied. Fibroblasts from a patient with a similar balanced reciprocal translocation but normal reproductive capabilities were also studied. Two of the four patients were found to have serologically detectable H-Y antigen on their cells. Since H-Y antigen has been found on the cells of other patients with X chromosome abnormalities but without a Y chromosome, it is thought that the X chromosome plays a role in the regulation of H-Y antigen expression. This study suggests that the long arm of the X chromosome may be involved but the location of a regulatory gene cannot be identified in these studies. These cases do not permit us to implicate H-Y antigen as a cause of gonadal dysgenesis and early gonadal failure in females who have structurally abnormal X chromosomes. 相似文献