全文获取类型
收费全文 | 914篇 |
免费 | 34篇 |
出版年
2023年 | 3篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 11篇 |
2019年 | 9篇 |
2018年 | 18篇 |
2017年 | 13篇 |
2016年 | 18篇 |
2015年 | 20篇 |
2014年 | 32篇 |
2013年 | 59篇 |
2012年 | 67篇 |
2011年 | 61篇 |
2010年 | 36篇 |
2009年 | 38篇 |
2008年 | 63篇 |
2007年 | 74篇 |
2006年 | 64篇 |
2005年 | 67篇 |
2004年 | 74篇 |
2003年 | 59篇 |
2002年 | 47篇 |
2001年 | 8篇 |
2000年 | 11篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 12篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有948条查询结果,搜索用时 593 毫秒
91.
Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. 相似文献
92.
Junko Morimoto Kento Hirabayashi Emu Mizumoto Takehiko Katsuno Yukihiro Morimoto 《Landscape and Ecological Engineering》2011,7(2):185-193
To develop an appropriate method of conservation for native Rhododendron sections Brachycalyx and Tsutsusi, the symbol of Satoyama, field experiments were performed in the dry granite region of Japan. When carpet-type landscape
of native rhododendrons was desired, all plants were cut at 20 cm above the ground level of all trees and shrubs, and herbs
and ferns were weeded (once and three times, respectively). When shrubby-type landscape of native rhododendrons was desired,
all plants, excluding native rhododendrons, were cut at 20 cm above the ground level of all trees and shrubs, herbs and ferns
were weeded, and litter was swept. After 3 years of monitoring of the percentage and depth of crowns with flower buds, the
following major results were obtained: Cutting all plants excluding native rhododendrons was effective to maintain the depth
of crowns with flower buds. However, weeding and sweeping of litter on the ground caused desiccation of surface soil, which
induced a transitory decrease in the percentage of crowns with flower buds. One weeding was effective in maintaining the depth
of crowns with flower buds; however, the second and third weedings had no distinct effect. In dry granite regions, considerable
attention to desiccation of surface soil is critical, as opposed to limiting attention to maintenance of sunlight as is common
practice. 相似文献
93.
Hiyoshi H Kodama T Saito K Gotoh K Matsuda S Akeda Y Honda T Iida T 《Cell host & microbe》2011,10(4):401-409
Vibrio parahaemolyticus, a Gram-negative halophilic bacterium that causes acute gastroenteritis in humans, is characterized by two type III secretion systems (T3SS), namely T3SS1 and T3SS2. T3SS2 is indispensable for enterotoxicity but the effector(s) involved are unknown. Here, we identify VopV as a critical effector that is required to mediate V. parahaemolyticus T3SS2-dependent enterotoxicity. VopV was found to possess multiple F-actin-binding domains and the enterotoxicity caused by VopV correlated with its F-actin-binding activity. Furthermore, a T3SS2-related secretion system and a vopV homologous gene were also involved in the enterotoxicity of a non-O1/non-O139 V. cholerae strain. These results indicate that the F-actin-targeting effector VopV is involved in enterotoxic activity of T3SS2-possessing bacterial pathogens. 相似文献
94.
95.
Lasley RD Keith BJ Kristo G Yoshimura Y Mentzer RM 《American journal of physiology. Heart and circulatory physiology》2005,289(2):H785-H791
Adenosine A1 receptor delayed preconditioning (PC) against myocardial infarction has been well described; however, there have been limited investigations of the signaling mechanisms that mediate this phenomenon. In addition, there are multiple conflicting reports on the role of inducible nitric oxide synthase (iNOS) in mediating A1 late-phase PC. The purpose of this study was to determine the roles of the p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs) in in vivo delayed A1 receptor PC and whether this protection at the myocyte level is due to upregulation of iNOS. Myocardial infarct size was measured in open-chest anesthetized rats 24 h after treatment with vehicle or the adenosine A1 agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 100 microg/kg ip). Additional rats receiving CCPA were pretreated with the p38 inhibitor SB-203580 (1 mg/kg ip) or the MAPK/ERK kinase (MEK) inhibitor PD-098059 (0.5 mg/kg ip). At 24 h after CCPA administration, a group of animals was given the iNOS inhibitor 1400 W 10 min before ischemia. Treatment with CCPA reduced infarct size from 48 +/- 2 to 28 +/- 2% of the area at risk, an effect that was blocked by both SB-203580 and PD-098059 but not 1400 W. Ventricular myocytes isolated 24 h after CCPA injection exhibited significantly reduced oxidative stress during H2O2 exposure compared with myocytes from vehicle-injected animals, and this effect was not blocked by the iNOS inhibitor 1400 W. Western blot analysis of whole heart and cardiac myocyte protein samples revealed no expression of iNOS 6 or 24 h after CCPA treatment. These results indicate that adenosine A1 receptor delayed PC in rats is mediated by MAPK-dependent mechanisms, but this phenomenon is not associated with the early or late expression of iNOS. 相似文献
96.
Fujita Y Yamaguchi K Kamegaya T Sato H Semura K Mutoh K Kashimoto T Ohori H Mukai T 《Helicobacter》2005,10(6):567-576
BACKGROUND: Helicobacter pylori survival in a hostile acidic environment is known to be caused by its production of urease, which is not released by known secretion pathways. It has been proposed that H. pylori cells undergo spontaneous autolysis during cultivation and that urease becomes surface-associated only concomitant with bacterial autolysis. The aim of this study was to elucidate mechanisms by which H. pylori cells undergo autolysis during cultivation. MATERIALS AND METHODS: Autolysis of H. pylori KZ109 cells was estimated by measuring the turbidity of the culture, by detection of cytoplasmic protein release into the culture supernatant and by scanning electron microscopic observation of H. pylori cells during cultivation. An autolysis-inducing factor (AIF) was partially purified from the culture supernatant by a partition method using ethyl acetate. RESULTS: Bacterial turbidity of KZ109 cells was drastically decreased after late-log phase accompanying release of urease and HspB into the extracellular space. Concomitantly, cell lytic activity was detected in the culture supernatant. Scanning electron microscopic observation suggested that partially purified AIF induced cell lysis. It was also shown that the AIF is different from other autolytic enzymes or substances so far reported. CONCLUSIONS: This study demonstrated the presence of the peptidergic autolytic substances in the culture supernatant of H. pylori KZ109 cells. The results of this study should be useful for further studies aimed at elucidation of the strategy of survival of H. pylori in the gastric environment and elucidation of the mechanisms of pathogenesis induced by H. pylori. 相似文献
97.
98.
99.
Hoshino S Yoshida M Inoue K Yano Y Yanagita M Mawatari H Yamane H Kijima T Kumagai T Osaki T Tachiba I Kawase I 《Biochemical and biophysical research communications》2005,329(1):58-63
Cigarette smoking is the most crucial factor responsible for chronic obstructive pulmonary disease (COPD). The precise mechanisms of the development of the disease have, however, not been fully understood. Recently, impairment of pulmonary endothelial cells has been increasingly recognized as a critical pathophysiological process in COPD. To verify this hypothesis, we examined how cigarette smoke extract (CSE) damages human umbilical vein endothelial cells (HUVECs). CSE activated c-Jun N-terminal kinase (JNK), and treatment of HUVECs with SP600125, a specific inhibitor of the JNK pathway, significantly suppressed endothelial cell damage by CSE. In contrast, inhibition of the extracellular-regulated kinase or the p38 pathway did not affect the cytotoxicity of CSE. Furthermore, anti-oxidants superoxide dismutase and catalase reduced CSE-induced JNK phosphorylation and endothelial cell injury. These results indicate that CSE damages vascular endothelial cells through the JNK pathway activated, at least partially, by oxidative stress. 相似文献
100.
Antiangiogenic photodynamic therapy (PDT) by using long-circulating liposomes modified with peptide specific to angiogenic vessels 总被引:4,自引:0,他引:4
Ichikawa K Hikita T Maeda N Yonezawa S Takeuchi Y Asai T Namba Y Oku N 《Biochimica et biophysica acta》2005,1669(1):69-74
For the improvement of therapeutic efficacy in photodynamic therapy (PDT) by using a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), we previously prepared polyethylene glycol (PEG)-modified liposomes encapsulating BPD-MA (PEG-Lip BPD-MA). PEGylation of liposomes enhanced the accumulation of BPD-MA in tumor tissue at 3 h after injection of it into Meth-A-sarcoma-bearing mice, but, unexpectedly, decreased the suitability of the drug for PDT when laser irradiation was performed at 3 h after the injection of the liposomal photosensitizer. To improve the bioavailability of PEG-Lip BPD-MA, we endowed the liposomes with active-targeting characteristics by using Ala-Pro-Arg-Pro-Gly (APRPG) pentapeptide, which had earlier been isolated as a peptide specific to angiogenic endothelial cells. APRPG-PEG-modified liposomal BPD-MA (APRPG-PEG-Lip BPD-MA) accumulated in tumor tissue similarly as PEG-Lip BPD-MA and to an approx. 4-fold higher degree than BPD-MA delivered with non-modified liposomes at 3 h after the injection of the drugs into tumor-bearing mice. On the contrary, unlike the treatment with PEG-Lip BPD-MA, APRPG-PEG-Lip BPD-MA treatment strongly suppressed tumor growth after laser irradiation at 3 h after injection. Finally, we observed vasculature damage in the dorsal air sac angiogenesis model by APRPG-PEG-Lip BPD-MA-mediated PDT. The present results suggest that antiangiogenic PDT is an efficient modality for tumor treatment and that tumor neovessel-targeted, long-circulating liposomes are a useful carrier for delivering photosensitizer to angiogenic endothelial cells. 相似文献