全文获取类型
收费全文 | 227篇 |
免费 | 16篇 |
专业分类
243篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 6篇 |
2020年 | 3篇 |
2019年 | 9篇 |
2018年 | 6篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 11篇 |
2013年 | 17篇 |
2012年 | 12篇 |
2011年 | 16篇 |
2010年 | 4篇 |
2009年 | 24篇 |
2008年 | 16篇 |
2007年 | 17篇 |
2006年 | 6篇 |
2005年 | 17篇 |
2004年 | 13篇 |
2003年 | 13篇 |
2002年 | 16篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1987年 | 1篇 |
排序方式: 共有243条查询结果,搜索用时 15 毫秒
21.
Shiina I Sano Y Nakata K Suzuki M Yokoyama T Sasaki A Orikasa T Miyamoto T Ikekita M Nagahara Y Hasome Y 《Bioorganic & medicinal chemistry》2007,15(24):7599-7617
Two new synthetic pathways to the anti-cancer agent tamoxifen and its derivatives were developed. The first route involved the aldol reaction of benzyl phenyl ketone with acetaldehyde followed by Friedel–Crafts substitution with anisole in the presence of Cl2Si(OTf)2 to produce 1,1,2-triaryl-3-acetoxybutane, a precursor of the tamoxifen derivatives. The second one utilized the novel three-component coupling reaction among aromatic aldehydes, cinnamyltrimethylsilane, and aromatic nucleophiles using HfCl4 as a Lewis acid catalyst to produce 3,4,4-triarylbutene, that is also a valuable intermediate of the tamoxifen derivatives. The former strategy requires a total of 10 steps from the aldol formation to the final conversion to tamoxifen, whereas the latter needs only three or four steps to produce tamoxifen and droloxifene including the installation of the side-chain moiety and the base-induced double-bond migration to form the tetra-substituted olefin structure. This synthetic strategy seems to serve as a new and practical pathway to prepare not only the tamoxifen derivatives but also the other SERMs (selective estrogen receptor modulators) including estrogen-dependent breast cancer and osteoporosis agents. 相似文献
22.
23.
24.
Tsukasa Ikemura Akane Miyaji Hideaki Kashima Yuji Yamaguchi Naoyuki Hayashi 《Journal of physiological anthropology》2013,32(1):23
Background
Heat stress induces various physiological changes and so could influence ocular circulation. This study examined the effect of heat stress on ocular blood flow.Findings
Ocular blood flow, end-tidal carbon dioxide (PETCO2) and blood pressure were measured for 12 healthy subjects wearing water-perfused tube-lined suits under two conditions of water circulation: (1) at 35°C (normothermia) for 30 min and (2) at 50°C for 90 min (passive heat stress). The blood-flow velocities in the superior temporal retinal arteriole (STRA), superior nasal retinal arteriole (SNRA), and the retinal and choroidal vessels (RCV) were measured using laser-speckle flowgraphy. Blood flow in the STRA and SNRA was calculated from the integral of a cross-sectional map of blood velocity. PETCO2 was clamped at the normothermia level by adding 5% CO2 to the inspired gas. Passive heat stress had no effect on the subjects’ blood pressures. The blood-flow velocity in the RCV was significantly lower after 30, 60 and 90 min of passive heat stress than the normothermic level, with a peak decrease of 18 ± 3% (mean ± SE) at 90 min. Blood flow in the STRA and SNRA decreased significantly after 90 min of passive heat stress conditions, with peak decreases of 14 ± 3% and 14 ± 4%, respectively.Conclusion
The findings of this study suggest that passive heat stress decreases ocular blood flow irrespective of the blood pressure or arterial partial pressure of CO2. 相似文献25.
Akane Sueki Kazuyuki Matsuda Chinami Iwashita Chiaki Taira Nau Ishimine Shohei Shigeto Kenji Kawasaki Mitsutoshi Sugano Hiroshi Yamamoto Takayuki Honda 《Biochemical and biophysical research communications》2014
Epithelial–mesenchymal transition (EMT) is associated with pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF). In this study, we investigated EMT of human pulmonary epithelial-derived cells (A549). A549 cells was either cultured by itself or co-cultured with THP-1 macrophages under normoxic (21% O2) and hypoxic (2% O2) conditions. We evaluated the presence of EMT by determining the expression of EMT markers, E-cadherin, vimentin, and fibronectin. To determine the role of TGF-β1 and IL-1β in EMT of the A549 cells, we analyzed the effects of blocking their activity with TGF-β1 inhibitor or IL-1β neutralizing antibody respectively. The A549 cells presented EMT when they were co-cultured with THP-1 macrophages. The EMT of the A549 cells co-cultured with THP-1 macrophages was exacerbated under hypoxia. In addition, the EMT were prevented by the addition of TGF-β1 type I receptor kinase inhibitor. The hypoxic condition increased the mRNA levels of TGF-β1 in A549 cells and THP-1 macrophages and that of IL-1β in THP-1 macrophages when each cells were co-cultured. Anti-IL-1β neutralizing antibody attenuated TGF-β1 secretion in co-culture media under hypoxic conditions. Thus, the IL-1β from THP-1 macrophages up-regulated the TGF-β1 from A549 cells and THP-1 macrophages, and then the TGF-β1 from both cells induced and promoted the EMT of A549 cells when they were co-cultured under hypoxia. Together, these results demonstrate that the interaction between type II pneumocytes and macrophages under hypoxia is necessary for the development of pulmonary fibrosis. 相似文献
26.
Yusuke Kosugi Asami Matsuoka Akane Higashi Noriko Toyohara Shigeru Satoh 《Journal of Plant Biology》2014,57(4):218-224
2-Aminooxyisobutyric acid (AOIB) has a partial structure of aminooxyacetic acid (AOA) in its whole structure, and resembles 2-aminoisobutyric acid (AIB) in their tetrahedral structures. Both AOA and AIB are inhibitors of ethylene biosynthesis; AOA inhibits the action of 1-aminocyclopropane-1-carboxylate (ACC) synthase and AIB inhibits that of ACC oxidase. The present study showed that AOIB inhibited the in vitro activities of both ACC synthase and ACC oxidase, which were synthesized heterologously in E. coli cells from corresponding carnation cDNAs, and the magnitudes of inhibition were similar to those caused by AOA and AIB; AOIB and AOA at 0.1 mM inhibited ACC synthase action by 75%, and AOIB and AIB at 10 mM inhibited ACC oxidase action by 16.3 and 22.5%, respectively. AOIB at 1 mM caused 91.5% reduction of maximum ethylene production rate as compared to the control in cut ‘Excerea’ carnation flowers undergoing senescence, thereby lengthening their vase life to 7 d from 3 d of the control flowers. The inhibition by AOIB was probably caused by its action resembling AOA, but not AIB. AOIB also extended significantly the vase life of cut flowers of ‘Pax’ carnation, and tended to do so in ‘Primero Mango’ carnation. The present findings suggest the potential of AOIB as a new preservative for carnations and other ornamentals in which ethylene plays a key role in the induction of senescence. 相似文献
27.
Exposure to high‐concentration oxygen in the neonatal period induces abnormal retinal vascular patterning in mice 下载免费PDF全文
Akane Morita Hiroko Ushikubo Asami Mori Kenji Sakamoto Tsutomu Nakahara 《Birth defects research. Part B, Developmental and reproductive toxicology》2016,107(6):216-224
The interruption of vascular development could cause structural and functional abnormalities in tissues. We have previously reported that short‐term treatment of newborn mice with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors induces abnormal retinal vascular growth and patterns. An exposure of neonatal mice to high‐concentration oxygen disturbs normal retinal vascular development. The present study aimed to determine (1) whether vascular abnormalities are observed in the retina of newborn mice exposed to high concentrations of oxygen, and (2) how astrocyte network formation is affected following the exposure to hyperoxia. Newborn (postnatal day 0) mice were exposed to 75% oxygen for 48 or 96 hr. During hyperoxia exposure, VEGF expression decreased, and the onset of retinal vascularization was completely suppressed. After completion of the hyperoxic period, retinal vascularization occurred, but it was delayed in a hyperoxic exposure duration‐dependent manner. In retinas of hyperoxia‐exposed mice, dense capillary plexuses were found, and the number of arteries and veins decreased. The astrocyte network formation was slightly delayed under hyperoxic conditions, and the network became denser in retinas of mice with an episode of hyperoxia. Expression of VEGF levels in the avascular retina of mice that were exposed to hyperoxia was higher than that of control mice. These results suggest that short‐term interruption of the onset of vascular development resulting from the reduction in VEGF signals induces abnormal vascular patterns in the mouse retina. The abnormalities in retinal astrocyte behavior might contribute to the formation of an abnormal retinal vascular growth. 相似文献
28.
29.
Hosokawa H Kimura MY Shinnakasu R Suzuki A Miki T Koseki H van Lohuizen M Yamashita M Nakayama T 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(11):7656-7664
The Polycomb group (PcG) gene products regulate the maintenance of the homeobox gene expression in Drosophila and vertebrates and also the cell cycle progression in thymocytes and Th2 cell differentiation in mature T cells. We herein studied the role of PcG gene bmi-1 product in Th1/Th2 cell differentiation and found that Bmi-1 facilitates Th2 cell differentiation in a Ring finger-dependent manner. Biochemical studies indicate that Bmi-1 interacts with GATA3 in T cells, which is dependent on the Ring finger of Bmi-1. The overexpression of Bmi-1 resulted in a decreased ubiquitination and an increased protein stability of GATA3. In bmi-1-deficient Th cells, the levels of Th2 cell differentiation decreased as the degradation and ubiquitination on GATA3 increased. Therefore, Bmi-1 plays a crucial role in the control of Th2 cell differentiation in a Ring finger-dependent manner by regulating GATA3 protein stability. 相似文献
30.
Treatment of Mid‐Pregnant Mice with KRN633, an Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase,Induces Abnormal Retinal Vascular Patterning in Their Newborn Pups 下载免费PDF全文
Akane Morita Tsutomu Nakahara Naomichi Abe Asami Mori Kenji Sakamoto Tohru Nagamitsu Kunio Ishii 《Birth defects research. Part B, Developmental and reproductive toxicology》2014,101(4):293-299
We previously reported that treatment of mid‐pregnant mice with KRN633, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, caused fetal growth restriction resulting from diminished vascularization in the placenta and fetal organs. In this study, we examined how the treatment of mid‐pregnant mice with KRN633 affects the development and morphology of vascular components (endothelial cells, pericytes, and basement membrane) in the retinas of their newborn pups. Pregnant mice were treated with KRN633 (5 mg/kg) once daily from embryonic day 13.5 until the day of delivery. Vascular components were examined using immunohistochemistry with specific markers for each component. Radial vascular growth in the retina was slightly delayed until postnatal day 4 (P4) in the newborn pups of KRN633‐treated mothers. On P8, compared with the pups of control mothers, the pups of KRN633‐treated mothers exhibited decreased numbers of central arteries and veins and abnormal branching of the central arteries. No apparent differences in pericytes or basement membrane were observed between the pups of control and KRN633‐treated mothers. These results suggest that a critical period for determining retinal vascular patterning is present at the earliest stages of retinal vascular development, and that the impaired vascular endothelial growth factor signaling during this period induces abnormal architecture in the retinal vascular network 相似文献