全文获取类型
收费全文 | 5665篇 |
免费 | 874篇 |
国内免费 | 365篇 |
专业分类
耳鼻咽喉 | 15篇 |
儿科学 | 27篇 |
妇产科学 | 45篇 |
基础医学 | 1249篇 |
口腔科学 | 119篇 |
临床医学 | 219篇 |
内科学 | 1110篇 |
皮肤病学 | 56篇 |
神经病学 | 543篇 |
特种医学 | 74篇 |
外科学 | 307篇 |
综合类 | 820篇 |
现状与发展 | 2篇 |
预防医学 | 119篇 |
眼科学 | 130篇 |
药学 | 1018篇 |
中国医学 | 390篇 |
肿瘤学 | 661篇 |
出版年
2024年 | 61篇 |
2023年 | 216篇 |
2022年 | 360篇 |
2021年 | 505篇 |
2020年 | 393篇 |
2019年 | 376篇 |
2018年 | 334篇 |
2017年 | 364篇 |
2016年 | 368篇 |
2015年 | 459篇 |
2014年 | 466篇 |
2013年 | 416篇 |
2012年 | 365篇 |
2011年 | 340篇 |
2010年 | 239篇 |
2009年 | 215篇 |
2008年 | 196篇 |
2007年 | 151篇 |
2006年 | 99篇 |
2005年 | 91篇 |
2004年 | 74篇 |
2003年 | 57篇 |
2002年 | 44篇 |
2001年 | 37篇 |
2000年 | 28篇 |
1999年 | 42篇 |
1998年 | 52篇 |
1997年 | 37篇 |
1996年 | 41篇 |
1995年 | 25篇 |
1994年 | 27篇 |
1993年 | 25篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 27篇 |
1989年 | 36篇 |
1988年 | 14篇 |
1987年 | 18篇 |
1986年 | 11篇 |
1985年 | 34篇 |
1984年 | 38篇 |
1983年 | 22篇 |
1982年 | 22篇 |
1981年 | 24篇 |
1980年 | 19篇 |
1979年 | 15篇 |
1978年 | 23篇 |
1977年 | 14篇 |
1976年 | 15篇 |
1975年 | 9篇 |
排序方式: 共有6904条查询结果,搜索用时 15 毫秒
991.
992.
Long non‐coding RNA AGER‐1 functionally upregulates the innate immunity gene AGER and approximates its anti‐tumor effect in lung cancer 下载免费PDF全文
993.
Downregulation of reticulocalbin‐1 differentially facilitates apoptosis and necroptosis in human prostate cancer cells 下载免费PDF全文
Xiaofei Liu Nianzhao Zhang Dawei Wang Deyu Zhu Quan Yuan Xiulei Zhang Lilin Qian Huanmin Niu Yi Lu Guijie Ren Keli Tian Huiqing Yuan 《Cancer science》2018,109(4):1147-1157
Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)‐resident Ca2+‐binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase‐dependent manner but mainly causes necroptosis in LNCaP cells. An animal‐based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy. 相似文献
994.
Cytoplasmic liver kinase B1 promotes the growth of human lung adenocarcinoma by enhancing autophagy 下载免费PDF全文
Mengjie Liu Lili Jiang Xiao Fu Wenjuan Wang Jiequn Ma Tao Tian Kejun Nan Xuan Liang 《Cancer science》2018,109(10):3055-3067
Liver kinase B1 (LKB1) as a tumor suppression gene that is associated with various kinds of cancers, including lung cancer. In this study, we found that the effect of LKB1 on tumor growth was dependent on its subcellular expression in A549 and HCC827 cells. Full‐length LKB1 decreased the proliferation and clonogenicity of A549‐LKB1 and HCC827‐LKB1 cells, but increased their apoptosis. Opposite effects were observed in A549‐LKB1s and HCC827‐LKB1S cells that overexpressed truncated LKB1 without the nuclear localization sequence. The truncated cytoplasmic LKB1 enhanced the growth of implanted tumors in vivo. The truncated cytoplasmic LKB1 promoted autophagy, which was independent of AMP‐activated protein kinase and mTOR signaling in A549 and HCC827 cells. Further characterization indicated that higher levels of cytoplasmic LKB1 expression were associated with advanced TNM stage and reduced overall survival (OS) in 190 patients with adenocarcinoma. In contrast, high nuclear expression of LKB1 is associated with early TNM stage and longer OS. The high level of cytoplasmic LKB1 expression was an independent risk factor for poor overall survival in patients with adenocarcinoma. Together, our results revealed that cytoplasmic LKB1 promotes the growth of lung adenocarcinoma and could be a prognostic marker for lung adenocarcinoma. 相似文献
995.
Summary Conspicuous dilatations and inclusions of the rough endoplasmic reticulum have been observed within the cytoplasm of sheath cells (cells of Schwann) and connective tissue in cat sympathetic ganglia. The sheath cell inclusions have been found regularly in young animals (under 6 weeks of age), and in older specimens following partial preganglionic nerve section. Electron-density of the inclusion material is characteristic for each kind of cell.Three possible functional roles are suggested for the material observed in the dilated sacs of sheath cells: (a) for manufacture of the basement membrane (b) for participating in the nutrition of nerve processes (c) for providing lipoprotein required for myelination of axons. It is also entirely possible that the cell utilizes this product in a variety of ways. The ER inclusions of connective tissue cells are thought to function in the synthesis of collagen.Present knowledge does not permit analysis of the mechanisms responsible for controlling this secretory machinery. 相似文献
996.
We investigated the effect of altering internal free magnesium concentration (Mgi) on the contraction and Cai transient of patch-clamped rabbit ventricular myocytes. Experiments were performed at 35°C; cells were held at –40 mV to
inactivate Na channels and T-type Ca channels, and at this potential (and in the absence of cyclic AMP) ”Ca-induced Ca release”
is the primary trigger mechanism. Cells dialysed with a low Mgi (2.9 μM) had a large and fast phasic contraction and Cai transient at positive potentials (+60, +80 mV). Cells dialysed with a high Mgi (7.1 mM) had a small or absent phasic contraction and Cai transient at positive potentials. These effects were due to a change in free Mgi, and not due to a change in [Mg.ATP]. In cells dialysed with a low Mgi, application of Ca channel blockers (32 μM nifedipine with 10 μM D600) for a single beat abolished current through L-type
Ca channels (I
Ca,L); however, 53% of the Cai transient was still elicited. Adding 5 mM Ni to Ca channel blockers abolished the remaining Cai transient, indicating that (in the absence of I
Ca,L) the transient might be triggered by reverse Na/Ca exchange. In cells dialysed with a high Mgi, a single-beat switch to Ca channel blockers was sufficient alone to abolish the Cai transient, indicating that under these conditions Ca entry via I
Ca,L is the primary sarcoplasmic reticulum trigger mechanism. These results suggest that raised free Mgi might partially inhibit the activity of the Na/Ca exchange, or might limit its ability to trigger Ca release.
Received: 29 August 1997 / Received after revision: 12 November 1997 / Accepted: 13 November 1997 相似文献
997.
G. G. Du C. C. Ashley T. J. Lea 《Pflügers Archiv : European journal of physiology》1994,429(2):169-175
Thapsigargin has been reported to inhibit ATP-dependent Ca2+ uptake by isolated sarcoplasmic reticulum (SR) vesicles of vertebrate skeletal muscle fibres at nanomolar concentrations. There have been no reports confirming this effect in skinned muscle fibre preparations. We have examined the ability of thapsigargin to inhibit the uptake of Ca2+ by the SR in mechanically skinned fibres of frog iliofibularis muscles, using the size of the caffeine-induced contracture to assess the Ca2+ content of the SR. The SR was first depleted of Ca2+ and then reloaded for 1 min at pCa 6.2 in the presence and absence of thapsigargin. When 5 min were allowed for diffusion, a thapsigargin concentration of at least 131 M was required to inhibit Ca2+ loading by 50%. In contrast, another SR Ca2+ uptake inhibitor, cyclopiazonic acid, was more effective, producing 50% inhibition at 7.0 M and total inhibition at 50 M. When cyclopiazonic acid (100 M) was applied after, rather than during, Ca2+ loading, the caffeine-induced contracture was not changed. Thapsigargin (300 M), on the other hand, caused some reduction in the peak amplitude of the caffeine-induced contracture when applied after Ca2+ loading. The poor effectiveness of thapsigargin in the skinned fibres, compared with in SR vesicles, is attributed to its slow diffusion into the skinned fibres, perhaps as a result of binding to myofibrillar components. 相似文献
998.
Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine 总被引:4,自引:0,他引:4
CD8(+) T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc(18-27), was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C(18-27) encoding gene. ERTS fusion significantly enhanced specific CD8(+) T cell responses in terms of CTL cytolysis as well as IFN-gamma secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine. 相似文献
999.
目的: 探讨以重组腺相关病毒(rAAV)为载体的心肌肌浆网Ca2+-ATP酶(SERCA2a)基因转导对慢性心力衰竭犬心功能的影响。方法: 选取成年比格犬17只,随机分为对照组4只和心力衰竭组11只。快速右心室起搏建立慢性心力衰竭犬模型并随机分为心力衰竭组4只、心力衰竭+绿色荧光蛋白(EGFP)组4只、心力衰竭+SERCA2a组5只(其中1只在开胸后死亡)。接受基因导入的心力衰竭犬行开胸术,分别向心肌内注射携带EGFP和SERCA2a基因的rAAV载体。于基因转导30d时停止起搏后进行超声心动图和血流动力学检查。结果: 基因转导30 d时,心力衰竭+SERCA2a 组犬的症状及超声心动图指标与心力衰竭+EGFP组相比有显著好转(P<0.05);与对照组相比无显著差别。血流动力学监测发现,转导SERCA2a的犬LVSP、+dp/dtmax和-dp/dtmax明显升高,平均值较EGFP组分别增加54.12%[(214.72±31.74)mmHg vs (139.32±36.79)mmHg]、146.81%[(6 779.43±217.58)mmHg/s vs (2 746.85±931.23)mmHg/s]和71.52%[(-4 341.42±322.02)mmHg/s vs (-2 531.14±616.15 mmHg/s)],LVEDP则降低了63.43%[(21.86±6.95)mmHg vs (59.78±6.92)mmHg],所有参数与对照组相比无显著差异。心力衰竭+EGFP组犬心肌冰冻切片在激光共聚焦显微镜下可见弥漫绿色荧光。结论: 以rAAV为载体介导SERCA2a基因转导能够改善慢性心力衰竭犬心脏的收缩和舒张功能,是1种有前景的治疗慢性心力衰竭的方法。 相似文献
1000.