全文获取类型
收费全文 | 2058篇 |
免费 | 123篇 |
国内免费 | 31篇 |
专业分类
耳鼻咽喉 | 7篇 |
儿科学 | 37篇 |
妇产科学 | 10篇 |
基础医学 | 279篇 |
口腔科学 | 45篇 |
临床医学 | 131篇 |
内科学 | 633篇 |
皮肤病学 | 32篇 |
神经病学 | 142篇 |
特种医学 | 130篇 |
外科学 | 279篇 |
综合类 | 4篇 |
预防医学 | 68篇 |
眼科学 | 47篇 |
药学 | 124篇 |
中国医学 | 7篇 |
肿瘤学 | 237篇 |
出版年
2023年 | 23篇 |
2022年 | 74篇 |
2021年 | 105篇 |
2020年 | 63篇 |
2019年 | 73篇 |
2018年 | 63篇 |
2017年 | 50篇 |
2016年 | 72篇 |
2015年 | 88篇 |
2014年 | 84篇 |
2013年 | 78篇 |
2012年 | 134篇 |
2011年 | 144篇 |
2010年 | 81篇 |
2009年 | 48篇 |
2008年 | 95篇 |
2007年 | 103篇 |
2006年 | 90篇 |
2005年 | 97篇 |
2004年 | 100篇 |
2003年 | 76篇 |
2002年 | 81篇 |
2001年 | 54篇 |
2000年 | 45篇 |
1999年 | 39篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 17篇 |
1995年 | 15篇 |
1994年 | 17篇 |
1993年 | 8篇 |
1992年 | 18篇 |
1991年 | 13篇 |
1990年 | 17篇 |
1989年 | 15篇 |
1988年 | 13篇 |
1987年 | 16篇 |
1986年 | 9篇 |
1985年 | 13篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 2篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有2212条查询结果,搜索用时 15 毫秒
1.
Yuki Izawa Masanori Yoshizumi Keisuke Ishizawa Yoshiko Fujita Shuji Kondo Shoji Kagami Kazuyoshi Kawazoe Koichiro Tsuchiya Shuhei Tomita Toshiaki Tamaki 《Hypertension research》2007,30(11):1107-1117
Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling. 相似文献
2.
Abstract: This study was investigated to clarify the role of intracellular Ca2+ following endotoxin treatment (1 mg/kg, intraperitoneally) to D-galactosamine-sensitized mice (400 mg/kg, intraperitoneally), and to observe lipid peroxide levels, an index of hepatotoxicity, in endotoxin/galactosamine (Ga1N)-challenged mice under activation of macrophages, especially Kupffer cells, by zymosan. The liver lipid peroxide level and serum glutamic pyruvic transminase activity in mice 18 hr after administration of endotoxin/Ga1N were markedly higher than those in mice treated only with endotoxin. In spite of an increase in lipid peroxide formation, there was little or no effect of Ga1N administration on xanthine oxidase and superoxide dismutase activities in mice given endotoxin. However, the injection of verapamil (10 mg/kg, subcutaneously) markedly decreased lipid peroxide levels in liver of endotoxin/Ga1N-injected mice. In the mice given a Ca2+-deficient diet, lipid peroxide level in liver after endotoxin/Ga1N injection was markedly decreased compared to that in mice fed a normal diet. Administration of dexamethasone (200 μg/kg, intraperitoneally) in mice 1 hr before treatment with endotoxin/Ga1N did not induce lipid peroxide formation. Administration of endotoxin to Ga1N-treated mice resulted in a higher level of liver cytosolic free Ca2+ ([Ca2+]i) than that in endotoxin-treated mice. On the other hand, Ca2+-ATPase activity in liver plasma membrane in the endotoxin/Ga1N-treated mice was markedly decreased as compared with endotoxin alone. On the contrary, the Ca2+-ATPase activity in liver mitochondria was higher in endotoxaemic mice treated with Ga1N than in mice given endotoxin alone. State 3 respiration and respiratory control index, which are parameters of mitochondrial function, were decreased more in the liver of mice treated with endotoxin/Ga1N than in the endotoxin-treated group. These findings suggest that [Ca2+]i may participate in the lipid peroxide formation which results from endotoxin/Ga1N-induced hepatotoxicity under conditions of zymosan-activated macrophages, and that the increases of endotoxin-sensitivity caused by Ga1N challenge may greatly contribute to Ca2+-mobilization in the hepatocyte. 相似文献
3.
Shinichiro Yasumoto Jun Tsujita Shuhei Imayama Yoshiaki Hori 《The Journal of dermatology》1996,23(7):499-501
We report a case of Gianotti-Crosti syndrome associated with human herpesvirus-6 (HHV-6) infection. An eight-month-old girl developed monomorphous papules on her cheeks, buttocks, and extremities after the subsidence of exanthema subitum. Viral antibody analysis confirmed primary HHV-6 infection. HHV-6 may be added to the list of causative agents of Gianotti-Crosti syndrome. 相似文献
4.
T. Terada K. Miyamoto G. Hyotani M. Tsuura Y. Nakamura T. Nishiguchi T. Itakura S. Hayashi N. Komai 《Acta neurochirurgica》1992,118(3-4):108-111
Summary Changes in tumour blood flow under an induced hypertensive state were examined in malignant brain tumours to know if the precondition for the effectiveness of induced hypertensive chemotherapy — relative increase in tumour blood flow — are fulfilled. Tumour blood flow was measured under both a resting and an induced hypertensive state in 12 patients with various malignant brain tumours (6 gliomas, 6 metastatic brain tumours) using xenon-enhanced computed tomography. The blood pressure was elevated 40% above the systemic blood pressure of the resting state by the infusion of angiotensin II. Tumour blood flow increased 30% on average above the normal brain tissue blood flow after the induction of an induced hypertensive state (p < 0.05). The tumour blood flow increased in 11 cases of malignant tumours, but decreased in one case with massive brain oedema after induced hypertension. The increase in blood flow was higher in hypervascular tumours and less in hypovascular tumours. Therefore, induced hypertensive chemotherapy probably will be more effective in hypervascular malignant brain tumours with small mass effects. 相似文献
5.
A technique for reducing the morbidity and mortality of pancreatoduodenectomy by using an omental flap to protect the anastomoses and splanchnic vessels exposed during dissection is described herein. 相似文献
6.
7.
8.
Yoshitaka Hibino Ken-ichiro Hata Kunio Horie Shuhei Torii Minoru Ueda 《Journal of cranio-maxillo-facial surgery》1996,24(6):346-351
Numerous clinical reports have shown the utility of cultured epithelial grafting in the field of plastic and reconstructive surgery. Recently, freezing storage of the cultured epithelium has been tried and has successfully grafted after thawing. It is clinically convenient if it is possible for cultured epithelium to keep its normal structure and viability. However, few papers have described the structural changes in cultured epithelium after freezing storage. In the present study, the morphological changes and cell viability of cultured mucosal epithelial sheets after freezing were studied in comparison with cultured epidermal sheets. Furthermore, we discuss the effect of storage temperature and cryoprotectants.As a result, there were some structural changes such as vacuolar degeneration in the cultured mucosal sheets using dimethyl sulphoxide (DMSO) as a cryoprotectant. Such changes were more clearly observed at −80°C than at −196°C with DMSO. However, little morphological change was observed in both epithelial sheets cultured with glycerin. The cell viability analysed by flow cytometry showed that more than 62% of the cells kept their viability after freezing storage. These results suggest that the optimum conditions of freezing for cultured epithelium were −196°C storage by slow cooling methods with glycerin as a cryoprotectant. 相似文献
9.
Boxall S Stanton T Hirai K Ward V Yasui T Tahara H Tamori A Nishiguchi S Shiomi S Ishiko O Inaba M Nishizawa Y Dawes R Bodmer W Beverley PC Tchilian EZ 《Human molecular genetics》2004,13(20):2377-2384
The CD45 antigen is a haemopoietic cell specific tyrosine phosphatase essential for antigen receptor mediated signalling in lymphocytes. Expression of different patterns of alternatively spliced CD45 isoforms is associated with distinct functions. We recently identified a polymorphism in exon 6 (A138G) of the gene encoding CD45 (PTPRC) that results in altered CD45 splicing. The 138G allele is present at a high frequency among Japanese (23.7%), with 5.1% individuals homozygous for the G allele. In this study we show that the A138G polymorphism is the cause of altered CD45 isoform expression, promoting splicing towards low molecular weight CD45 isoforms. We further report that the frequency of A138G heterozygotes is significantly reduced in number in cohorts of patients with autoimmune Graves' disease or hepatitis B infection, whereas G138G homozygotes are absent from a cohort of Hashimoto's thyroiditis patients. We also show that 138G individuals exhibit altered cytokine production in vitro and an increased proportion of memory T cells. These data suggest that the 138G variant allele strongly influences these diseases by modulation of immune mechanisms and may have achieved its high frequency as a result of a natural selection probably related to pathogen resistance. 相似文献
10.
Kazutaka Suga Minori Saitoh Satoshi Kokubo Kazutoshi Nozaki Shinji Fukushima Shuhei Yasuda Masao Sasamata Keiji Miyata 《Journal of interferon & cytokine research》2004,24(6):343-349
Recombinant human interleukin-11 (rHuIL-11) and recombinant human bone morphogenetic protein-2 (rHuBMP-2) have been shown to act synergistically in the induction of osteoblast differentiation. To determine whether these two proteins can be used clinically in fracture healing and reconstructive surgery, we investigated whether rHuIL-11 and rHuBMP-2 act synergistically to heal segmental bone defects in a rabbit model. A 1.5-cm segmental defect was created in the right ulnar diaphysis of 20 Japanese white rabbits. Polylactic-co-glycolic acid (PLGA)-coated gelatin sponges (PGS) permeated with rHuBMP-2 (n = 8), rHuIL-11 plus rHuBMP-2 (n = 8), or rHuIL-11 (n = 4) were implanted into the bone defects. Radiographs were scored by two independent observers for bone formation and union rates after 2, 3, 4, and 8 weeks. Bone formation was higher in rabbits implanted with rHuBMP-2 plus rHuIL-11 than in those implanted with rHuBMP-2 alone, reaching statistical significance after 4 weeks. At early time points, the union rate in rabbits implanted with rHuBMP-2 plus rHuIL-11 was higher than in rabbits implanted with rHuBMP-2. At 2, 4, and 8 weeks, new bone volume was significantly higher in rabbits administered rHuIL-11 plus rHuBMP-2 than in those given rHuBMP-2 alone. In contrast, mechanical testing after 8 weeks showed that bone strength in the two groups of rabbits was equivalent. These findings show that rHuIL-11 and rHuBMP-2 act synergistically to accelerate bone formation without affecting bone strength. Treatment with a combination of rHuIL-11 and rHuBMP-2 may thus be of great benefit in fracture healing and for patients undergoing reconstructive surgery. 相似文献