全文获取类型
收费全文 | 333篇 |
免费 | 17篇 |
专业分类
耳鼻咽喉 | 75篇 |
儿科学 | 3篇 |
妇产科学 | 12篇 |
基础医学 | 26篇 |
口腔科学 | 2篇 |
临床医学 | 26篇 |
内科学 | 36篇 |
皮肤病学 | 1篇 |
神经病学 | 9篇 |
特种医学 | 8篇 |
外科学 | 32篇 |
综合类 | 8篇 |
预防医学 | 15篇 |
眼科学 | 3篇 |
药学 | 72篇 |
中国医学 | 2篇 |
肿瘤学 | 20篇 |
出版年
2021年 | 4篇 |
2020年 | 3篇 |
2019年 | 7篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 11篇 |
2014年 | 7篇 |
2013年 | 15篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 5篇 |
2009年 | 6篇 |
2008年 | 7篇 |
2007年 | 11篇 |
2006年 | 16篇 |
2005年 | 22篇 |
2004年 | 11篇 |
2003年 | 13篇 |
2002年 | 9篇 |
2001年 | 5篇 |
2000年 | 8篇 |
1999年 | 4篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1992年 | 5篇 |
1991年 | 10篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1979年 | 6篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 2篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1972年 | 7篇 |
1971年 | 5篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1967年 | 4篇 |
1966年 | 1篇 |
1965年 | 2篇 |
排序方式: 共有350条查询结果,搜索用时 0 毫秒
61.
62.
63.
64.
65.
66.
Huang Y Blower PE Liu R Dai Z Pham AN Moon H Fang J Sadée W 《Pharmaceutical research》2007,24(9):1702-1712
Purpose A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting tumor growth is sufficient
intracellular drug accumulation. We hypothesized that membrane transporters on tumor cells determine at least in part the
response to GA analogues.
Materials and Methods To facilitate a systematic study of chemosensitivity across a group of GA analogues with similar chemical structures, we correlated
mRNA expression profiles of most known transporters with growth inhibitory potencies of compounds in 60 tumor cell lines (NCI-60).
We subsequently validated the gene-drug correlations using cytotoxicity and transport assays.
Results Geldanamycin analogues displayed a range of negative correlations coefficients with ABCB1 (MDR1, or P-glycoprotein) expression.
Suppressing ABCB1 in multidrug resistant cells (NCI/ADR-RES and K562/DOX) and ABCB1-transfected cells (BC19) increased sensitivity
to GA analogues, as expected for substrates. Moreover, ABCB1-mediated efflux of daunorubicin in K562/DOX cells could be blocked
markedly by GA analogues in a dose-dependent fashion. The IC50 values (half-maximum inhibition of daunorubicin efflux) were 5.5, 7.3 and 12 μM for macbecin II (NSC330500), 17-AAG (NSC330507)
and GA, respectively.
Conclusions These observations demonstrate that GA analogues are substrates as well as inhibitors of ABCB1, suggesting that drug interactions
between GA analogues and other agents that are ABCB1 substrates may occur via ABCB1 in normal or tumor cells.
Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users. 相似文献
67.
Winau F Weber S Sad S de Diego J Hoops SL Breiden B Sandhoff K Brinkmann V Kaufmann SH Schaible UE 《Immunity》2006,24(1):105-117
CD8 T lymphocytes are important effectors in protective immunity against Mycobacterium tuberculosis. We recently characterized the detour pathway of CD8 T cell activation in tuberculosis mediated by apoptotic vesicles from infected cells that transport mycobacterial antigens to dendritic cells (DCs). Here we demonstrate that apoptotic vesicles from mycobacteria-infected macrophages stimulate CD8 T cells in vivo. Homing of DCs to draining lymph nodes was critically required for effective crosspriming. Subsequent fate of vesicle-associated antigens in recipient DCs was characterized by endosomal mechanisms predominating over proteasomal processing. In addition, vesicle processing depended on the presence of saposins to disintegrate apoptotic membranes. Apoptotic vesicles displayed potent adjuvant activity by stimulating through Toll-like receptors (TLR). Ultimately, vaccination with vesicles from infected cells induced protection against M. tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis. 相似文献
68.
Endobronchial tuberculosis is defined as tuberculosis infection of tracheobronchial tree and it is not seen often in adult population. In the absence of parenchymal disease endobronchial tuberculosis is less well-recognized and can lead to difficulties in diagnosis. Our aim is to introduce a rare form of tuberculosis that is important because of high probability of developing severe bronchostenosis during its course. We report a 20-year-old woman who presented with two-month history of severe non-productive cough, shortness of breath, and hemoptysis. After clinical and radiological evaluation, flexible bronchoscopy showed bilateral multiple tumorous lesions that were seen from main carina down to the both main bronchus. The biopsy samples revealed EBTB diagnosis and antituberculosis therapy was given. At the second month of the therapy, rebronchoscopy revealed almost disappearance of the polypoid lesions. The patient healed without any stenosis. This case report is a reminder that endobronchial tuberculosis must take into consideration in differential diagnosis of endobronchial lesions. In patients with endobronchial tuberculosis healing without any complication could be achieved with timely diagnosis and commencement of early treatment. 相似文献
69.
Mycobacterium bovis BCG-infected mice are more susceptible to staphylococcal enterotoxin B-mediated toxic shock than uninfected mice despite reduced in vitro splenocyte responses to superantigens
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Pedras-Vasconcelos JA Chapdelaine Y Dudani R van Faassen H Smith DK Sad S 《Infection and immunity》2002,70(8):4148-4157
Type 1 T-cell responses against intracellular pathogens play a crucial role in mediating protection. We examined whether the induction of a strong type 1 T-cell response during a chronic bacterial infection influences responses to superantigens capable of inducing acute shock. Intravenous infection of mice with Mycobacterium bovis BCG appeared to induce a progressive anergy towards staphylococcal enterotoxin B (SEB) and towards antigen preparation of BCG (BCG-Ag) itself, based on diminished gamma interferon (IFN-gamma) production by SEB- and BCG-Ag-stimulated splenocytes from infected mice. In contrast to these in vitro results, injection of SEB into BCG-infected mice led to a dramatic increase in the serum IFN-gamma levels and the death of infected but not of control mice. In vitro hyporesponsiveness towards SEB and BCG-Ag occurred only with unfractionated splenocyte cultures, as purified T cells from infected mice produced higher levels of IFN-gamma. Hyporesponsiveness towards SEB and BCG-Ag in unfractionated splenocyte cultures was not due to suppressive antigen-presenting cells (APCs), as APCs from infected mice stimulated higher levels of IFN-gamma from purified T cells. The diminished IFN-gamma levels observed with bulk splenocytes appear to be due to changes in the T-cell-to-APC ratio that result in a decreased proportion of T cells, coupled to reduced proliferative responses and an increased susceptibility of effector T cells to activation-induced cell death in vitro. Our results indicate that the reported phenomena of T-cell anergy during mycobacterial infection may be an in vitro consequence of the development of a strong type 1 response in vivo. 相似文献
70.