全文获取类型
收费全文 | 537篇 |
免费 | 40篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 6篇 |
妇产科学 | 6篇 |
基础医学 | 85篇 |
口腔科学 | 9篇 |
临床医学 | 42篇 |
内科学 | 121篇 |
皮肤病学 | 22篇 |
神经病学 | 54篇 |
特种医学 | 15篇 |
外科学 | 60篇 |
综合类 | 10篇 |
预防医学 | 31篇 |
眼科学 | 3篇 |
药学 | 73篇 |
肿瘤学 | 34篇 |
出版年
2022年 | 5篇 |
2021年 | 6篇 |
2020年 | 11篇 |
2019年 | 8篇 |
2018年 | 5篇 |
2017年 | 5篇 |
2016年 | 13篇 |
2015年 | 11篇 |
2014年 | 9篇 |
2013年 | 12篇 |
2012年 | 17篇 |
2011年 | 26篇 |
2010年 | 11篇 |
2009年 | 14篇 |
2008年 | 17篇 |
2007年 | 19篇 |
2006年 | 25篇 |
2005年 | 27篇 |
2004年 | 19篇 |
2003年 | 21篇 |
2002年 | 16篇 |
2001年 | 19篇 |
2000年 | 19篇 |
1999年 | 16篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 16篇 |
1991年 | 18篇 |
1990年 | 15篇 |
1989年 | 14篇 |
1988年 | 11篇 |
1987年 | 10篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 5篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1975年 | 9篇 |
1974年 | 7篇 |
1973年 | 8篇 |
1972年 | 4篇 |
1971年 | 4篇 |
1969年 | 4篇 |
排序方式: 共有577条查询结果,搜索用时 15 毫秒
101.
We studied whether noradrenaline release is affected by interleukin-1β and the neuropeptides urotensin II, melanin-concentrating hormone (MCH), neuropeptide W (NPW) and neuropeptide FF (NPFF). Rodent tissues preincubated with [3H]noradrenaline were superfused, and the effect of peptides on the electrically-evoked tritium overflow ("noradrenaline release") was studied. In mouse brain cortex, interleukin-1β at 0.3 nM and the prostaglandin E2 analogue sulprostone at 3 nM inhibited noradrenaline release by about 40% the effect of interleukin-1β developed gradually, whereas the effect of sulprostone occurred promptly. Urotensin II at 0.001-1 μM did not affect noradrenaline release in rat kidney cortex, whereas 0.01 μM angiotensin II increased it (positive control). MCH at 0.01-1 μM did not alter noradrenaline release in the rat brain cortex, and NPW 1 μM did not affect noradrenaline release in the mouse hypothalamus or hippocampus. In each model, 0.1 μM sulprostone inhibited noradrenaline release (positive control). NPFF and the NPFF2 receptor agonist dNPA (1 μM) did not affect noradrenaline release in the mouse atria; the inhibitory effect of the δ opioid receptor agonist 1 μM DPDPE on noradrenaline release in this tissue was not altered by NPFF or dNPA at 0.32 μM but was counteracted by the δ opioid antagonist naltrindole at 0.001 μM. In conclusion, interleukin-1β inhibits noradrenaline release in the mouse cortex; the effect develops gradually, suggesting that it affects protein biosynthesis. Noradrenergic neurons in various tissues from rodents are devoid of presynaptic receptors for urotensin II, MCH, NPW and NPFF. Finally, an interaction between a δ opioid agonist and NPFF could not be detected. 相似文献
102.
Schultz-Thater E Piscuoglio S Iezzi G Le Magnen C Zajac P Carafa V Terracciano L Tornillo L Spagnoli GC 《International journal of cancer. Journal international du cancer》2011,129(5):1137-1148
MAGE-A10 is a highly immunogenic member of the MAGE-A family of cancer/testis tumor-associated antigens (C/T TAAs). Studies performed with broadly reactive antibodies have helped to initially characterize this TAA. However, no specific reagents have been developed so far, thus preventing a thorough analysis of its expression in healthy and tumoral tissues. We have produced MAGE-A10 gene product in soluble recombinant form, and we have used it to generate specific monoclonal antibodies (mAbs). One of these reagents, recognizing an epitope located at the COOH terminus of the MAGE-A10 gene product, was used to stain a multitumor tissue microarray comprising more than 2,500 paraffin-embedded specimens including healthy tissues, benign tumors and malignancies of different histological origin. MAGE-A10 protein was identified as an intranuclear protein of an apparent molecular weight of 70 kDa, expressed in normal spermatogonia and spermatocytes but in no other healthy tissue. Most importantly, this C/T TAA appears to be expressed in high (>50%) percentages of cancer cells from a number of malignancies, including lung, skin and urothelial tumors. Unexpectedly, high expression of MAGE-A10 TAA at the protein level was also detectable in gynecological malignancies and stomach and gall bladder cancers. The characterization of MAGE-A10-specific reagents might set the stage for the development of targeted active immunotherapy by clarifying potential indications and by allowing the selection of patients eligible for treatment and the monitoring of its effectiveness. 相似文献
103.
Hamel N Feng BJ Foretova L Stoppa-Lyonnet D Narod SA Imyanitov E Sinilnikova O Tihomirova L Lubinski J Gronwald J Gorski B Hansen Tv Nielsen FC Thomassen M Yannoukakos D Konstantopoulou I Zajac V Ciernikova S Couch FJ Greenwood CM Goldgar DE Foulkes WD 《European journal of human genetics : EJHG》2011,19(3):300-306
The BRCA1 mutation c.5266dupC was originally described as a founder mutation in the Ashkenazi Jewish (AJ) population. However, this mutation is also present at appreciable frequency in several European countries, which raises intriguing questions about the origins of the mutation. We genotyped 245 carrier families from 14 different population groups (Russian, Latvian, Ukrainian, Czech, Slovak, Polish, Danish, Dutch, French, German, Italian, Greek, Brazilian and AJ) for seven microsatellite markers and confirmed that all mutation carriers share a common haplotype from a single founder individual. Using a maximum likelihood method that allows for both recombination and mutational events of marker loci, we estimated that the mutation arose some 1800 years ago in either Scandinavia or what is now northern Russia and subsequently spread to the various populations we genotyped during the following centuries, including the AJ population. Age estimates and the molecular evolution profile of the most common linked haplotype in the carrier populations studied further suggest that c.5266dupC likely entered the AJ gene pool in Poland approximately 400-500 years ago. Our results illustrate that (1) BRCA1 c.5266dupC originated from a single common ancestor and was a common European mutation long before becoming an AJ founder mutation and (2) the mutation is likely present in many additional European countries where genetic screening of BRCA1 may not yet be common practice. 相似文献
104.
Stephen R. Cole Ian Zajac Tess Gregory Sarah Mehaffey Naomi Roosa Deborah Turnbull Adrian Esterman Graeme P. Young 《International journal of behavioral medicine》2011,18(4):302-309
Background
Population screening reduces mortality from colorectal cancer, yet factors associated with uptake of screening are incompletely understood. 相似文献105.
Characterization of the single-cell transcriptional landscape by highly multiplex RNA-seq 总被引:1,自引:0,他引:1
Islam S Kjällquist U Moliner A Zajac P Fan JB Lönnerberg P Linnarsson S 《Genome research》2011,21(7):1160-1167
106.
107.
Wojciechowski S Jordan MB Zhu Y White J Zajac AJ Hildeman DA 《European journal of immunology》2006,36(7):1694-1706
Following an acute T cell response, most activated effector cells die, while some survive and become memory cells. The pro-apoptotic Bcl-2 family member, Bcl-2 interacting mediator of death (Bim) is critical for eliminating most effector T cells, while expression of CD127 (IL-7Ralpha) has been proposed to mark effector cells destined to become memory cells. Here, we examined the effects of Bim on the death of effector T cells in relationship to CD127 expression and on development of T cell memory following lymphocytic choriomeningitis virus (LCMV) infection. We found that large numbers of CD127(lo) LCMV-specific CD4(+) and CD8(+) T cells were lost in wild-type mice, but were spared in Bim(-/-) mice. Further, while the numbers of CD127(hi) T cells declined only slightly during contraction of the response in wild-type mice, they increased significantly in Bim(-/-) mice due to re-expression of CD127 on CD127(lo) T cells that had avoided apoptosis. Functional memory T cells were significantly increased in Bim(-/-) mice; however, they underwent a slow attrition due to decreased proliferative renewal. Taken together, these data suggest that the absence of Bim-mediated death of LCMV-specific CD4(+) and CD8(+) T cells in vivo can increase T cell memory, but other homeostatic mechanisms control the long-term maintenance of memory cells. 相似文献
108.
Weber WP Feder-Mengus C Chiarugi A Rosenthal R Reschner A Schumacher R Zajac P Misteli H Frey DM Oertli D Heberer M Spagnoli GC 《European journal of immunology》2006,36(2):296-304
Production of indoleamine 2,3-dioxygenase (IDO) by tumor cells, leading to tryptophan depletion and production of immunosuppressive metabolites, may facilitate immune tolerance of cancer. IDO gene is also expressed in dendritic cells (DC) upon maturation induced by lipopolysaccarides or IFN. We investigated IDO gene expression in melanoma cell lines and clinical specimens as compared to mature DC (mDC). Furthermore, we explored effects of L-kynurenine (L-kyn) and 3-hydroxyanthranilic acid (3-HAA) on survival and antigen-dependent and independent proliferation of CD8(+) cells. We observed that IDO gene expression in cultured tumor cells and freshly excised samples is orders of magnitude lower than in mDC, providing highly efficient antigen presentation to CD8(+) T cells. Non toxic concentrations of L-kyn or 3-HAA did not significantly inhibit antigen-specific CTL responses. However, 3-HAA, but not L-kyn markedly inhibited antigen-independent proliferation of CD8(+) T cells induced by common receptor gamma-chain cytokines IL-2, -7 and -15. Our data suggest that CD8(+) T cell activation induced by antigenic stimulation, a function exquisitely fulfilled by mDC, is unaffected by tryptophan metabolites. Instead, in the absence of effective T cell receptor triggering, 3-HAA profoundly affects homeostatic proliferation of CD8(+) T cells. 相似文献
109.
110.