全文获取类型
收费全文 | 5403篇 |
免费 | 332篇 |
国内免费 | 46篇 |
专业分类
耳鼻咽喉 | 64篇 |
儿科学 | 84篇 |
妇产科学 | 27篇 |
基础医学 | 704篇 |
口腔科学 | 69篇 |
临床医学 | 485篇 |
内科学 | 1539篇 |
皮肤病学 | 115篇 |
神经病学 | 402篇 |
特种医学 | 120篇 |
外科学 | 979篇 |
综合类 | 13篇 |
预防医学 | 140篇 |
眼科学 | 30篇 |
药学 | 304篇 |
中国医学 | 12篇 |
肿瘤学 | 694篇 |
出版年
2023年 | 76篇 |
2022年 | 139篇 |
2021年 | 237篇 |
2020年 | 128篇 |
2019年 | 200篇 |
2018年 | 208篇 |
2017年 | 147篇 |
2016年 | 194篇 |
2015年 | 165篇 |
2014年 | 229篇 |
2013年 | 239篇 |
2012年 | 347篇 |
2011年 | 340篇 |
2010年 | 202篇 |
2009年 | 145篇 |
2008年 | 229篇 |
2007年 | 280篇 |
2006年 | 231篇 |
2005年 | 232篇 |
2004年 | 215篇 |
2003年 | 199篇 |
2002年 | 200篇 |
2001年 | 101篇 |
2000年 | 83篇 |
1999年 | 86篇 |
1998年 | 38篇 |
1997年 | 23篇 |
1996年 | 23篇 |
1995年 | 31篇 |
1994年 | 29篇 |
1993年 | 26篇 |
1992年 | 69篇 |
1991年 | 47篇 |
1990年 | 44篇 |
1989年 | 50篇 |
1988年 | 45篇 |
1987年 | 48篇 |
1986年 | 49篇 |
1985年 | 49篇 |
1984年 | 28篇 |
1983年 | 19篇 |
1982年 | 24篇 |
1979年 | 33篇 |
1978年 | 20篇 |
1977年 | 17篇 |
1972年 | 14篇 |
1971年 | 18篇 |
1969年 | 17篇 |
1968年 | 26篇 |
1967年 | 25篇 |
排序方式: 共有5781条查询结果,搜索用时 15 毫秒
101.
Tumor necrosis factor alpha-induced interleukin-8 production via NF-kappaB and phosphatidylinositol 3-kinase/Akt pathways inhibits cell apoptosis in human hepatocytes 总被引:3,自引:0,他引:3 下载免费PDF全文
Osawa Y Nagaki M Banno Y Brenner DA Asano T Nozawa Y Moriwaki H Nakashima S 《Infection and immunity》2002,70(11):6294-6301
Tumor necrosis factor alpha (TNF-alpha) not only induces apoptotic signals but also causes antiapoptotic and regenerative responses in the liver. However, the molecular mechanism(s) of the latter events remains unclear. In the present study, we examined TNF-alpha-induced genes in Hc human normal (unsensitized) hepatocytes by cDNA microarray analysis. Interleukin-8 (IL-8) induction was the most pronounced of the upregulated genes. The IL-8 protein level was also increased. IL-8 belongs to the ELR-CXC chemokine family and appears to exert mitogenic and antiapoptotic functions in other cell systems. IL-8 expression by TNF-alpha was inhibited when two survival signals, nuclear factor kappaB (NF-kappaB) and phosphatidylinositol 3-kinase (PI3K)/Akt, were inhibited by a mutant form of inhibitor of NF-kappaB (IkappaB); by dominant negative (kinase-dead) Akt; or by treatment with LY 294002, an inhibitor of PI3K. TNF-alpha induced apoptosis in Hc cells that were sensitized by inhibition of NF-kappaB and PI3K activation. IL-8 administration protected mice against concanavalin A-induced hepatitis in vivo. IL-8 also rescued the sensitized Hc cells, at least in part, from TNF-alpha-induced apoptosis in vitro. TNF-alpha inhibited DNA synthesis in unsensitized Hc cells in the absence of serum. Exogenous IL-8 reversed, though anti-IL-8 neutralization antibody enhanced, growth inhibition by TNF-alpha. These results indicate that IL-8, the production of which is stimulated by TNF-alpha, inhibits apoptosis of sensitized hepatocytes and releases normal (unsensitized) hepatocytes from growth inhibition induced by TNF-alpha. 相似文献
102.
Hirohito Sumikura Akihiko Homma Kentaro Ohnuma Yoshiyuki Taenaka Yoshiaki Takewa Hiroshi Mukaibayashi Kazuo Katano Eisuke Tatsumi 《Journal of artificial organs》2013,16(2):138-148
We developed a novel endurance test system that can arbitrarily set various circulatory conditions and has durability and stability for long-term continuous evaluation of ventricular assist devices (VADs), and we evaluated its fundamental performance and prolonged durability and stability. The circulation circuit of the present endurance test system consisted of a pulsatile pump with a small closed chamber (SCC), a closed chamber, a reservoir and an electromagnetic proportional valve. Two duckbill valves were mounted in the inlet and outlet of the pulsatile pump. The features of the circulation circuit are as follows: (1) the components of the circulation circuit consist of optimized industrial devices, giving durability; (2) the pulsatile pump can change the heart rate and stroke length (SL), as well as its compliance using the SCC. Therefore, the endurance test system can quantitatively reproduce various circulatory conditions. The range of reproducible circulatory conditions in the endurance test circuit was examined in terms of fundamental performance. Additionally, continuous operation for 6 months was performed in order to evaluate the durability and stability. The circulation circuit was able to set up a wide range of pressure and total flow conditions using the SCC and adjusting the pulsatile pump SL. The long-term continuous operation test demonstrated that stable, continuous operation for 6 months was possible without leakage or industrial device failure. The newly developed endurance test system demonstrated a wide range of reproducible circulatory conditions, durability and stability, and is a promising approach for evaluating the basic characteristics of VADs. 相似文献
103.
104.
Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis 总被引:4,自引:0,他引:4 下载免费PDF全文
Nishida M Fujinaka H Matsusaka T Price J Kon V Fogo AB Davidson JM Linton MF Fazio S Homma T Yoshida H Ichikawa I 《The Journal of clinical investigation》2002,110(12):1859-1868
We examined the in vivo function of the angiotensin II type 1 receptor (Agtr1) on macrophages in renal fibrosis. Fourteen days after the induction of unilateral ureteral obstruction (UUO), wild-type mice reconstituted with marrow lacking the Agtr1 gene (Agtr1(-/-)) developed more severe interstitial fibrosis with fewer interstitial macrophages than those in mice reconstituted with Agtr1(+/+) marrow. These differences were not observed at day 5 of UUO. The expression of profibrotic genes - including TGF-beta1, alpha1(I) collagen, and alpha1(III) collagen - was substantially higher in the obstructed kidneys of mice with Agtr1(-/-) marrow than in those with Agtr1(+/+) marrow at day 14 but not at day 5 of UUO. Mice with Agtr1(-/-) marrow were characterized by reduced numbers of peripheral-blood monocytes and macrophage progenitors in bone marrow. In vivo assays revealed a significantly impaired phagocytic capability in Agtr1(-/-) macrophages. In vivo treatment of Agtr1(+/+) mice with losartan reduced phagocytic capability of Agtr1(+/+) macrophages to a level comparable to that of Agtr1(-/-) macrophages. Thus, during urinary tract obstruction, the Agtr1 on bone marrow-derived macrophages functions to preserve the renal parenchymal architecture, and this function depends in part on its modulatory effect on phagocytosis. 相似文献
105.
Morio Y Homma N Takahashi H Yamamoto A Nagaoka T Sato K Muramatsu M Fukuchi Y 《Journal of vascular research》2007,44(4):325-335
The mechanism of endothelium-dependent vasodilator signaling involves three components such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). Although EDHF is distinct from nitric oxide and prostacyclin, it requires activation of Ca(2+)-sensitive K(+) channels (K(Ca)) and cytochrome P(450) metabolites. However, the physiological role of EDHF in the pulmonary circulation is unclear. Thus, we tested if EDHF would regulate vascular tone in rat lungs of control and monocrotaline (MCT)-induced pulmonary hypertension. Inhibition of EDHF with a combination of K(Ca) blockers, charybdotoxin (50 nM) plus apamin (50 nM), increased baseline vascular tone in MCT-induced hypertensive lungs. Thapsigargin (TG; 100 nM), an inhibitor of Ca-ATPase, caused greater EDHF-mediated vasodilation in MCT-induced hypertensive lungs. TG-induced vasodilation was abolished with the charybdotoxin-apamin combination. Sulfaphenazole (10 muM), a cytochrome P(450) inhibitor, reduced the TG-induced vasodilation in MCT-induced hypertensive lungs. RT-PCR analysis exhibited an increase in K(Ca) mRNA in MCT-treated lungs. These results indicate the augmentation of tonic EDHF activity, at least in part, through the alteration in cytochrome P(450) metabolites and the upregulation of K(Ca) expression in MCT-induced pulmonary hypertension. 相似文献
106.
Hiroshi Onimaru Akiko Arata Ikuo Homma 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1995,106(1):57-68
In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by perforated whole-cell recordings using the antibiotic nystatin. Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions. For blockade of chemical synaptic transmission, perfusate Ca2+ concentration was lowered to 0.2 mM and the Mg2+ concentration was increased to 5 mM. In Iow-Ca2+, high-Mg2+ solution (referred to here as low Ca), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type neurons showed periodic depolarization of 5–12 mV in low Ca, at a rate of 12±6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period. Thus, the burst generations were voltage dependent. The firing frequency of tonictype neurons was 2.3±1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization. Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity. Activity of C4 and Pre-I neurons was completely silent with 0.1–1 M tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type neurons (n=3) were also silent with 1 M TTX perfusion. Inspiratory neurons either became silent (n=4) or fired tonically (n=1) in low Ca. The present study by perforated whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs. 相似文献
107.
Hiromi Tateno MD PhD Ryuji Sakakibara MD PhD Shunsuke Shiina BSci Hirokazu Doi PhD Fuyuki Tateno MD PhD Mitsutoshi Sato PhD Tohru Masaka PhD Masahiko Kishi MD PhD Yohei Tsuyusaki MD Yosuke Aiba MD Tsuyoshi Ogata MSc Yasuo Suzuki MD PhD 《Journal of the American Geriatrics Society》2015,63(11):2416-2418
108.
109.
Koshiro Sonomoto Kunihiro Yamaoka Koichi Oshita Shunsuke Fukuyo Xiangmei Zhang Kazuhisa Nakano Yosuke Okada Yoshiya Tanaka 《Arthritis \u0026amp; Rheumatology》2012,64(10):3355-3363
Objective
Mesenchymal stem cells (MSCs) are considered to be a novel tool for the treatment of rheumatoid arthritis (RA) because of their multipotency to differentiate into osteoblasts and chondrocytes, their immunosuppressive effects, and availability. The aim of this study was to assess the mechanisms of human MSC differentiation into osteoblasts under inflammatory conditions.Methods
Human MSCs were cultured in commercialized osteogenic induction medium with inflammatory cytokines for up to 10 days. Osteoblast differentiation was detected by alkaline phosphatase staining and messenger RNA (mRNA) expression of multiple osteoblast markers. Mineralization was assessed by alizarin red S staining.Results
Among the various cytokines tested, interleukin‐1β (IL‐1β) induced differentiation of human MSCs into osteoblasts, which was confirmed by alkaline phosphatase activity, expression of RUNX2 mRNA, and strong alizarin red S staining. Among various molecules of the Wnt family, Wnt‐5a and receptor tyrosine kinase–like orphan receptor 2 (Ror2), a major receptor of Wnt‐5a, were significantly induced in human MSCs by IL‐1β. Silencing of either WNT5A or ROR2 by small interfering RNA with 2 different sequences reduced alkaline phosphatase activity, RUNX2 expression, and alizarin red S staining of human MSCs induced by IL‐1β.Conclusion
IL‐1β effectively and rapidly induced human MSC differentiation into osteoblasts and mineralization, mainly through the noncanonical Wnt‐5a/Ror2 pathway. These results suggest potential benefits of IL‐1β–treated human MSCs in the treatment of damaged bone as well as in the induction of self‐renewal and self‐repair of damaged tissue, including osseous tissue.110.
Mohamed Abdel-Wahab Mohammad Abdelghani Yosuke Miyazaki Erik W. Holy Constanze Merten Dirk Zachow Pim Tonino Marcel C.M. Rutten Frans N. van de Vosse Marie-Angele Morel Yoshinobu Onuma Patrick W. Serruys Gert Richardt Osama I. Soliman 《JACC: Cardiovascular Interventions》2018,11(3):287-297