全文获取类型
收费全文 | 350篇 |
免费 | 13篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 15篇 |
基础医学 | 70篇 |
口腔科学 | 9篇 |
临床医学 | 27篇 |
内科学 | 104篇 |
皮肤病学 | 1篇 |
神经病学 | 27篇 |
特种医学 | 2篇 |
外科学 | 45篇 |
综合类 | 1篇 |
预防医学 | 16篇 |
眼科学 | 3篇 |
药学 | 26篇 |
肿瘤学 | 17篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 8篇 |
2018年 | 8篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 7篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 16篇 |
2011年 | 15篇 |
2010年 | 10篇 |
2009年 | 13篇 |
2008年 | 20篇 |
2007年 | 20篇 |
2006年 | 26篇 |
2005年 | 21篇 |
2004年 | 29篇 |
2003年 | 33篇 |
2002年 | 26篇 |
2001年 | 7篇 |
2000年 | 1篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有369条查询结果,搜索用时 19 毫秒
91.
Yoshikazu Yuki Daisuke Tokuhara Tomonori Nochi Hiroshi Yasuda Mio Mejima Shiho Kurokawa Yuko Takahashi Nobuhiro Kataoka Ushio Nakanishi Yukari Hagiwara Kohtaro Fujihashi Fumio Takaiwa Hiroshi Kiyono 《Vaccine》2009
Rice-expressed cholera toxin B (CTB) subunit is a cold-chain-free oral vaccine that effectively induces enterotoxin-neutralising immunity. We created another rice-based vaccine, MucoRice, expressing nontoxic double-mutant cholera toxin (dmCT) with CTA and CTB subunits. Western-blot analysis suggested that MucoRice-dmCT had the shape of a multicomponent vaccine. Oral administration of MucoRice-dmCT induced CTB- but not CTA-specific serum IgG and mucosal IgA antibodies, generating protective immunity against cholera toxin without inducing rice-protein-specific antibody responses. The potency of MucoRice-dmCT was equal to that of MucoRice-CTB vaccine. MucoRice has the potential to be used as a safe multicomponent vaccine expression system. 相似文献
92.
Oi K Fukumoto Y Ito K Uwatoku T Abe K Hizume T Shimokawa H 《The Tohoku journal of experimental medicine》2008,214(2):151-158
We have recently demonstrated that the low-energy extracorporeal cardiac shock wave (SW) therapy improves myocardial perfusion and cardiac function in a porcine model of chronic myocardial ischemia and also ameliorates myocardial ischemia in patients with severe coronary artery disease. The present study was designed to examine whether our SW therapy also is effective to ameliorate hindlimb ischemia in rabbits. Hindlimb ischemia was made by surgical excision of the entire unilateral rabbit femoral artery. One week after the operation, we performed the SW (n = 9) or sham-therapy (n = 9) to the ischemic region 3 times a week for 3 weeks. Three weeks after the SW therapy, the development of collateral arteries, the flow ratio of the ischemic/non-ischemic common iliac arteries, the blood pressure ratio of the ischemic/non-ischemic hindlimb, and the capillary density in the ischemic muscles were all significantly increased in the SW group compared with the control group, indicating that the SW therapy induced therapeutic angiogenesis. Importantly, no adverse effect, such as muscle damage, hemorrhage, or thrombosis, was noted with the therapy. Finally, we examined the role of endothelial nitric oxide synthesis (eNOS) and vascular endothelial growth factor (VEGF) in the mechanisms of SW-induced angiogenesis on day 28. The expression levels of eNOS and VEGF proteins in ischemic hindlimb muscles tended to be increased in the SW group compared with the control group. These results suggest that our low-energy SW therapy also is effective and safe for the treatment of peripheral artery disease. 相似文献
93.
Extracorporeal cardiac shock wave therapy improves left ventricular remodeling after acute myocardial infarction in pigs 总被引:2,自引:0,他引:2
Uwatoku T Ito K Abe K Oi K Hizume T Sunagawa K Shimokawa H 《Coronary artery disease》2007,18(5):397-404
OBJECTIVE: We have recently demonstrated that low-energy extracorporeal shock wave therapy improves chronic myocardial ischemia in pigs and humans. In this study, we examined whether our shock wave therapy is also effective at improving left ventricular remodeling after acute myocardial infarction in pigs. METHODS: Acute myocardial infarction was created by surgically excising the proximal segment of the left circumflex coronary artery (n=20). In the early treatment protocol, the shock wave therapy was started 3 days after acute myocardial infarction, whereas in the late treatment protocol, the therapy was started 4 weeks after acute myocardial infarction (n=5 each). The remaining animals were treated in the same manner, but without the shock wave treatment in each protocol (n=5 each). RESULTS: In the early treatment protocol, left ventricular ejection fraction was higher (42+/-1 vs. 32+/-1%, P<0.001) and left ventricular end-diastolic volume was smaller (95+/-1 vs. 99+/-2 ml, P<0.05) in the shock wave group compared with the control group. Furthermore, wall thickening fraction (32+/-1 vs. 28+/-1%, P<0.01), regional myocardial blood flow (1.7+/-0.2 vs. 1.0+/-0.1 ml/min/g, P<0.01), and number of capillaries in the border zone (1348+/-15 vs. 938+/-34 mm2, P<0.0001) were all significantly improved in the shock wave group compared with the control group. By contrast, in the late treatment group, no such beneficial effects of the shock wave therapy were noted. CONCLUSION: These results suggest that our extracorporeal cardiac shock wave therapy is also an effective and noninvasive therapy for improving left ventricular remodeling after acute myocardial infarction when started in the early phase of the disorder. 相似文献
94.
Huang MC Okada M Nakatsu F Oguni H Ito M Morita K Nagafuji H Hirose S Sakaki Y Kaneko S Ohno H Kojima T 《Brain & development》2007,29(8):462-467
Evidence that some types of epilepsies show strong genetic predisposition has been well documented. AP3M2 is considered to be an epileptogenic gene because AP3M2 knockout mice exhibit symptoms of spontaneous epileptic seizures. In order to investigate whether the AP3M2 gene causes susceptibility to epilepsy, we performed mutation screening of the genomic DNA of 190 patients with six epilepsy types; this screening involved all the 9 exons and the relevant exon-intron boundaries of AP3M2. Although neither missense nor nonsense mutations were detected, we identified 21 sequence variations, of which 16 variations were novel. Of the 21 variations, 11 were detected in 5' and 3' UTRs, while the remaining variations were detected in introns. Although the present study failed to identify the possible AP3M2 mutations that may cause epilepsy, our results suggest that some AP3M2 mutations still remain candidates for unmapped disorders including epilepsy, febrile seizure, and other neuronal developmental disorders associated with functional abnormalities of GABAergic transmission. 相似文献
95.
96.
Yingzi Cong Ting Feng Kohtaro Fujihashi Trenton R. Schoeb Charles O. Elson 《Proceedings of the National Academy of Sciences of the United States of America》2009,106(46):19256-19261
A T cell receptor transgenic mouse line reactive to a microbiota flagellin, CBir1, was used to define mechanisms of host microbiota homeostasis. Intestinal IgA, but not serum IgA, was found to block mucosal flagellin uptake and systemic T cell activation in mice. Depletion of CD4+CD25+ Tregs decreased IgA+ B cells, total IgA, and CBir1-specific IgA in gut within days. Repletion of T cell-deficient mice with either CD4+CD25+ or CD4+foxp3+ Tregs restored intestinal IgA to a much greater extent than their reciprocal CD4+ subsets, indicating that Tregs are the major helper cells for IgA responses to microbiota antigens such as flagellin. We propose that the major role of this coordinated Treg-IgA response is to maintain commensalism with the microbiota. 相似文献
97.
Kohtaro Toyama Masamitsu Karasawa Arito Yamane Hiromi Koiso Akihiko Yokohama Hideki Uchiumi Takayuki Saitoh Hiroshi Handa Ken Sato Hitoshi Takagi Shuichi Miyawaki Hirokazu Murakami Yoshihisa Nojima Norifumi Tsukamoto 《International journal of hematology》2009,89(4):517-522
Approximately one-half of the cases of Budd-Chiari syndrome (BCS) are caused by bcr/abl negative chronic myeloproliferative
disorders (CMPDs). Furthermore, a mutation in the Janus kinase protein (JAK2-V617F) is detected in half of the patients with BCS. However, whether the JAK2 mutation is the primary event leading to CMPDs and
BCS is controversial. We present a report concerning a young woman who suffered from BCS prior to the onset of CMPDs. Analysis
of X-chromosome inactivation patterns in this patient, using the human androgen receptor gene demonstrated monoclonal haematopoiesis
in her granulocytes. In contrast, she had a low burden of a JAK2-V617F mutation positive clone among granulocyte populations. These results suggest that the JAK2-V617F mutation occurs after the onset of monoclonal haematopoiesis; thus the V617F mutation of JAK2 may not be the primary event
in the induction of BCS. 相似文献
98.
Saito A Yokohama A Osaki Y Ogawa Y Nakahashi H Toyama K Mitsui T Hashimoto Y Koiso H Uchiumi H Saitoh T Handa H Sawamura M Karasawa M Murakami H Tsukamoto N Nojima Y 《European journal of haematology》2012,88(4):340-349
Objectives: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by the production of autoreactive antibodies against platelet antigens. Although dysfunction of multiple aspects of cellular immunity is considered to be important in the pathogenesis of ITP, it has not been clarified which cell types play a principal role. Methods: We enrolled 46 untreated patients with chronic ITP and 47 healthy adult volunteers, and investigated by flow cytometry the percentage and absolute number of cells in their peripheral blood that participate in the regulation of cellular immunity. These included plasmacytoid dendritic cells (pDCs), myeloid dendritic cells (mDCs), natural killer (NK) cells, natural killer T (NKT) cells, regulatory T (Treg) cells, and Th17 cells. Results: We found a significant reduction in the absolute number of pDCs, but not of mDCs, in patients with ITP when compared with healthy controls (P < 0.001). Reduced numbers of circulating pDCs were observed in both Helicobacter pylori (H. pylori)‐positive and Helicobacter pylori (H. pylori)‐negative patients with ITP. In contrast, there were no significant differences in the numbers of circulating Treg cells, Th17 cells, NK cells, or NKT cells. Interestingly, we observed increases in the number of pDCs after H. pylori eradication by antibiotics in responders but not in non‐responders, while pDCs and mDCs decreased markedly after prednisolone therapy in both responders and non‐responders. In patients without treatment, low pDC numbers persisted during the observational period. Conclusions: We demonstrated that the number of circulating pDCs is low in patients with primary and H. pylori‐associated ITP and that it changes depending on treatment modality. Further investigation is warranted with regard to the role of pDCs in the immunopathogenesis of ITP. 相似文献
99.
Kato S Saeki Y Aoki M Nagai M Ishigaki A Itoyama Y Kato M Asayama K Awaya A Hirano A Ohama E 《Acta neuropathologica》2004,107(2):149-158
Living cells produce reactive oxygen species (ROSs). To protect themselves from these ROSs, the cells have developed both an antioxidant system containing superoxide dismutase 1 (SOD1) and a redox system including peroxiredoxin2 (Prx2, thioredoxin peroxidase) and glutathione peroxidase1 (GPx1): SOD1 converts superoxide radicals into hydrogen peroxide (H2O2), and H2O2 is then converted into harmless water (H2O) and oxygen (O2) by Prx2 and GPx1 that directly regulate the redox system. To clarify the biological significance of the interaction of the redox system (Prx2/GPx1) with SOD1 in SOD1-mutated motor neurons in vivo, we produced an affinity-purified rabbit antibody against Prx2 and investigated the immunohistochemical localization of Prx2 and GPx1 in neuronal Lewy body-like hyaline inclusions (LBHIs) in the spinal cords of familial amyotrophic lateral sclerosis (FALS) patients with a two-base pair deletion at codon 126 and an AlaVal substitution at codon 4 in the SOD1 gene, as well as in transgenic rats expressing human SOD1 with H46R and G93A mutations. The LBHIs in motor neurons from the SOD1-mutated FALS patients and transgenic rats showed identical immunoreactivities for Prx2 and GPx1: the reaction product deposits with the antibodies against Prx2 and GPx1 were localized in the LBHIs. In addition, the localizations of the immunoreactivities for SOD1 and Prx2/GPx1 were similar in the inclusions: the co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs in mutant SOD1-related FALS patients and transgenic rats was evident. Based on the fact that Prx2/GPx1 directly regulates the redox system, such co-aggregation of Prx2/GPx1 with SOD1 in neuronal LBHIs may lead to the breakdown of the redox system itself, thereby amplifying the mutant SOD1-mediated toxicity in mutant SOD1-linked FALS patients and transgenic rats expressing human mutant SOD1. 相似文献
100.
Hiroshi Fukuhara Masami Kuramochi Takeshi Fukami Kohtaro Kasahara Mutsuo Furuhata Takahiro Nobukuni Tomoko Maruyama Kana Isogai Takao Sekiya Taro Shuin Tadaichi Kitamura Roger H. Reeves Yoshinori Murakami 《Cancer science》2002,93(6):605-609
We recently identified TSLC1 , a tumor suppressor gene in human lung cancer. Gene silencing by promoter methylation has been observed frequently in adenocarcinoma of the lung, liver, and pancreas. Here, we demonstrate that TSLC1 expression is also absent or markedly reduced in 3 of 4 prostate cancer cell lines. Promoter sequences of TSLC1 were heavily methylated in PPC-1 cells that lacked TSLC1 expression, supporting the idea that promoter methylation is strongly correlated with complete loss of gene expression. Promoter sequences of TSLC1 were also methylated significantly in 7 of 22 (32%) primary prostate cancers. Hypermethylation of the promoter occurred not only in advanced tumors, but also in relatively early-stage tumors. Restoration of TSLC1 expression substantially suppressed tumor formation of PPC-1 cells in nude mice. These findings indicate that alteration of TSLC1 is involved in prostate cancer. 相似文献