全文获取类型
收费全文 | 348篇 |
免费 | 13篇 |
出版年
2021年 | 3篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 6篇 |
2014年 | 13篇 |
2013年 | 43篇 |
2012年 | 14篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 12篇 |
2008年 | 14篇 |
2007年 | 5篇 |
2006年 | 10篇 |
2005年 | 15篇 |
2004年 | 12篇 |
2003年 | 19篇 |
2002年 | 15篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 6篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 11篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有361条查询结果,搜索用时 312 毫秒
111.
H Abe N Iehara K Utsunomiya T Kita T Doi 《The Journal of biological chemistry》1999,274(30):20874-20878
Mesangial cells share features with contractile smooth muscle cells and mechanically support the capillary wall. The role of vitamin D compounds and the transforming growth factor-beta (TGF-beta) type II receptor in modulating the smooth muscle phenotype of cultured mesangial cells was examined. Cell proliferation was significantly inhibited by the vitamin D analog 22-oxa-1,25-dihydroxyvitamin D(3) (22-oxacalcitriol; OCT) rather than by 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) in a dose-dependent manner. OCT-treated early passage mesangial cells (MC-E cells) had increased expression levels of type IV collagen and smooth muscle alpha actin mRNA, but 1, 25(OH)(2)D(3)-treated MC-E cells did not. The addition of a TGF-beta(1)-neutralizing antibody to the OCT-treated MC-E cells blocked this inhibitory effect for cell proliferation and attenuated the up-regulated mRNA levels. However, after exposure to 1, 25(OH)(2)D(3) or OCT, there was no significant difference in the secretion of active TGF-beta. We next investigated whether TGF-beta type II receptor (RII) was involved in this regulation. OCT treatment significantly increased the expression of the RII mRNA in MC-E cells. These results suggest that the vitamin D analog OCT induces smooth muscle phenotypic alterations and that this phenomenon was mediated through the induction of RII in cultured mesangial cells. 相似文献
112.
Tamura M Utsunomiya H Nakamura M Landon EJ 《Canadian journal of physiology and pharmacology》2000,78(7):548-556
To investigate the possible physiological significance of dietary cardiac glycosides in blood pressure regulation, the blood pressure of normal Sprague Dawley rats raised on a regular diet, which naturally contains large amounts of Na+-pump inhibitors, was compared with that of rats on a purified synthetic diet, which contains no Na+-pump specific inhibitors, and with that of rats on a synthetic diet supplemented with 10 microg x mL(-1) ouabain or 10 microg x mL- convallatoxin in the drinking water. After 6 weeks on the synthetic diet, the systolic blood pressure in the synthetic diet group was significantly elevated (145 +/- 5 vs. 128 +/- 4 mmHg, P < 0.05). At 10 weeks it reached a plateau (154 +/- 3 vs. 122 +/- 3 mmHg, P < 0.05). Plasma renin activity and Na+ level were significantly higher in animals fed synthetic diets than in the regular diet group (P < 0.01). Administration of either losartan or lisinopril or a switch to a low salt synthetic diet (0.03% sodium) normalized the synthetic diet-induced high blood pressure. Supplementation of the synthetic diet with the cardiac glycosides delayed the onset of the increase in blood pressure for 4 weeks. Plasma aldosterone levels were approximately doubled in the cardiac glycoside-treated groups. Higher plasma Na+ levels and hematocrit values present in the synthetic diet group were normalized by the glycoside supplements. These results suggest that supplemental dietary cardiac glycosides exert bidirectional effects on blood pressure regulation through actions that modulate extracellular fluid and electrolyte balance. 相似文献
113.
The allene oxide synthase (AOS) was purified from corn (Zea mays) seeds to homogeneity and characterized partially. The corn AOS was a hemoprotein cytochrome P450 with a molecular weight and pI of 53,000 and 6.0, respectively. The corn AOS was found to be irreversibly inactivated by a substrate, 13-hydroperoxyoctadienoic acid. The rate of the enzyme inactivation was higher at low pHs. 相似文献
114.
Immunohistochemical study of NGF and its receptors in the synovial membrane of the ankle joint of adjuvant-induced arthritic rats 总被引:3,自引:1,他引:2
To study the role of nerve growth factor (NGF) in local inflammation, we investigated the expression of NGF and its receptors, trkA and p75, in the ankle joints of adjuvant-induced arthritic rats. Infiltrated mononuclear cells revealed a positive immunoreactivity for NGF and trkA; they were also positive for immunostaining for W3/25 and ED1, which mainly stain T cells and macrophages, respectively. Changes in the ratios of NGF-positive cells to mononuclear cells showed a relatively similar pattern for trkA-positive cells, which peaked at weeks 2 to 3 after the adjuvant injection. In double-immunofluorescence staining, 80% and 65% of NGF-positive cells stained for W3/25 and ED1, respectively. Similarly, 67% and 80% of trkA-positive cells also corresponded to W3/25- and ED1-positive cells, respectively. However, p75 immunoreactivity localized on the nerve fibers but not on the cells of the ankle joints. Dense meshworks of p75-positive nerve fibers with numerous terminal varicosities were observed at weeks 2 to 4. The present findings suggest that infiltrated mononuclear cells may secrete NGF in an autocrine or paracrine manner in the inflamed synovium. An upregulation of NGF in these mononuclear cells and an increase in density of the synovial nerve fibers may be involved in the development of adjuvant arthritis in rats. 相似文献
115.
Pharmacological profile of hydroxy fasudil as a selective rho kinase inhibitor on ischemic brain damage 总被引:7,自引:0,他引:7
Satoh S Utsunomiya T Tsurui K Kobayashi T Ikegaki I Sasaki Y Asano T 《Life sciences》2001,69(12):1441-1453
The neuroprotective property and the effects on hemodynamics of hydroxy fasudil, an active metabolite of an antispastic drug, fasudil, were examined. In rats, hydroxy fasudil was found following intravenous infusion or intraperitoneal administration of fasudil, and the maximum plasma concentration of hydroxy fasudil was approximately 25 or 40% of the parent drug, respectively. The i.v. administration of hydroxy fasudil produced significant increases in regional cerebral blood flow in dogs. Hydroxy fasudil relaxed the KCl, PGF2alpha or U-46619-induced contraction in canine basilar or middle cerebral arterial strips, concentration-dependently. The neuroprotective property of hydroxy fasudil was examined on delayed neuronal death in gerbils. Hydroxy fasudil (3 mg/kg) significantly protected against the ischemia-induced neuronal loss. To further clarify the effect on neurological impairments, hydroxy fasudil was tested in a rat model of microembolization stroke. Intravenous administration of hydroxy fasudil improved neurological functions, significantly reduced the size of the infarct area and prevented the accumulation of neutrophils. The present findings suggest that hydroxy fasudil has an efficacy to improve the hemodynamic function and to inhibit neutrophil-mediated damage, and contributes to the potency and long duration of the cytoprotective properties of fasudil on ischemic brain damage, and also suggest a critical role for rho kinase in the pathogenesis of cerebral ischemic injury, and the potential utility of rho kinase inhibitor as a therapeutic agent in stroke. 相似文献
116.
Matsuoka F Shinkai M Honda H Kubo T Sugita T Kobayashi T 《Biomagnetic research and technology》2004,2(1):3
BACKGROUND: We have developed magnetite cationic liposomes (MCLs) and applied them to local hyperthermia as a mediator. MCLs have a positive charge and generate heat under an alternating magnetic field (AMF) by hysteresis loss. In this study, the effect of hyperthermia using MCLs was examined in an in vivo study of hamster osteosarcoma. METHOD: MCLs were injected into the osteosarcoma and then subjected to an AMF. RESULTS: The tumor was heated at over 42 degrees C, but other normal tissues were not heated as much. Complete regression was observed in 100% of the treated group hamsters, whereas no regression was observed in the control group hamsters. At day 12, the average tumor volume of the treated hamsters was about 1/1000 of that of the control hamsters. In the treated hamsters, no regrowth of osteosarcomas was observed over a period of 3 months after the complete regression. CONCLUSION: These results suggest that this treatment is effective for osteosarcoma. 相似文献
117.
Kataoka Y Cui Y Yamada H Utsunomiya K Niiya H Yanase H Nakamura Y Mitani A Kataoka K Watanabe Y 《Biochemical and biophysical research communications》2000,273(2):637-641
Various kinds of acute pathological events in the central nervous system, such as ischemia, hemorrhage, and trauma, often cause brain edema. The edema may advance for days or weeks while inducing extensive damage in neural function, regardless of the extent of the original damage, and often results in death. Delayed edema is thought to be vasogenic; however, the mechanism underlying edema induction remains unknown. We found delayed vascular cell proliferation with a blood-brain barrier breakdown in and around the gerbil CA1 hippocampus, a region known to be involved in delayed apoptotic neuronal death 2-6 days after transient ischemia. Vascular cell proliferation, assessed by (3)H-thymidine incorporation, was most prominent 4-6 days after ischemia, and extravasation of exogenously applied dye or endogenous serum albumin from blood vessels was observed concomitantly. We propose neovascularization in delayed neuronal death as a cause of brain edema advancing days after neurological events. 相似文献
118.
119.
Noboru Shibasaki Toshinari Yamasaki Toru Kanno Ryuichiro Arakaki Hiromasa Sakamoto Noriaki Utsunomiya Takahiro Inoue Tatsuaki Tsuruyama Eijiro Nakamura Osamu Ogawa Tomomi Kamba 《PloS one》2015,10(6)
Vascular endothelial growth factor (VEGF) and mammalian target of rapamycin are well-known therapeutic targets for renal cell carcinoma (RCC). Sunitinib is an agent that targets VEGF receptors and is considered to be a standard treatment for metastatic or unresectable clear cell RCC (ccRCC). However, ccRCC eventually develops resistance to sunitinib in most cases, and the mechanisms underlying this resistance are not fully elucidated. In the present study, we established unique primary xenograft models, KURC1 (Kyoto University Renal Cancer 1) and KURC2, from freshly isolated ccRCC specimens. The KURC1 xenograft initially responded to sunitinib treatment, however finally acquired resistance. KURC2 retained sensitivity to sunitinib for over 6 months. Comparing gene expression profiles between the two xenograft models with different sensitivity to sunitinib, we identified interleukin 13 receptor alpha 2 (IL13RA2) as a candidate molecule associated with the acquired sunitinib-resistance in ccRCC. And patients with high IL13RA2 expression in immunohistochemistry in primary ccRCC tumor tends to have sunitinib-resistant metastatic site. Next, we showed that sunitinib-sensitive 786-O cells acquired resistance in vivo when IL13RA2 was overexpressed. Conversely, shRNA-mediated knockdown of IL13RA2 successfully overcame the sunitinib-resistance in Caki-1 cells. Histopathological analyses revealed that IL13RA2 repressed sunitinib-induced apoptosis without increasing tumor vasculature in vivo. To our knowledge, this is a novel mechanism of developing resistance to sunitinib in a certain population of ccRCC, and these results indicate that IL13RA2 could be one of potential target to overcome sunitinib resistance. 相似文献
120.
Laercio R Porto-Neto Tad S Sonstegard George E Liu Derek M Bickhart Marcos VB Da Silva Marco A Machado Yuri T Utsunomiya Jose F Garcia Cedric Gondro Curtis P Van Tassell 《BMC genomics》2013,14(1)