全文获取类型
收费全文 | 242篇 |
免费 | 25篇 |
专业分类
267篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 5篇 |
2018年 | 8篇 |
2017年 | 7篇 |
2016年 | 5篇 |
2015年 | 11篇 |
2014年 | 9篇 |
2013年 | 14篇 |
2012年 | 16篇 |
2011年 | 9篇 |
2010年 | 12篇 |
2009年 | 12篇 |
2008年 | 18篇 |
2007年 | 13篇 |
2006年 | 14篇 |
2005年 | 20篇 |
2004年 | 13篇 |
2003年 | 16篇 |
2002年 | 17篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 9篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1979年 | 1篇 |
1978年 | 2篇 |
排序方式: 共有267条查询结果,搜索用时 11 毫秒
191.
Kazushi Watanabe Akio Kakefuda Minoru Yasuda Kentaro Enjo Aya Kikuchi Takashi Furutani Yoichi Naritomi Yukio Otsuka Minoru Okada Mitsuaki Ohta 《Bioorganic & medicinal chemistry》2013,21(17):5261-5270
Type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5), also known as aldo-keto reductase 1C3 (AKR1C3), is a member of the aldo-keto reductase superfamily of enzymes and is expressed in the human prostate. One of the main functions of 17β-HSD5 is to catalyze the conversion of the weak androgen, androstenedione, to the potent androgen, testosterone. The concentration of intraprostatic 5α-dihydrotestosterone (DHT) in patients following chemical or surgical castration has been reported to remain as high as 39% of that of healthy men, with 17β-HSD5 shown to be involved in this androgen synthesis. Inhibition of 17β-HSD5 therefore represents a promising target for the treatment of castration-resistant prostate cancer (CRPC). To investigate this, we conducted high-throughput screening (HTS) and identified compound 2, which displayed a structure distinct from known 17β-HSD5 inhibitors. To optimize the inhibitory activity of compound 2, we first introduced a primary alcohol group. We then converted the primary alcohol group to a tertiary alcohol, which further enhanced the inhibitory activity, improved metabolic stability, and led to the identification of compound 17. Oral administration of compound 17 to castrated nude mice bearing the CWR22R xenograft resulted in the suppression of androstenedione (AD)-induced intratumoral testosterone production. Compound 17 also demonstrated good isoform selectivity, minimal inhibitory activity against either CYP or hERG, and enhanced pharmacokinetic and physicochemical properties. 相似文献
192.
193.
194.
Dermatopontin interacts with fibronectin, promotes fibronectin fibril formation, and enhances cell adhesion 总被引:1,自引:0,他引:1
Kato A Okamoto O Ishikawa K Sumiyoshi H Matsuo N Yoshioka H Nomizu M Shimada T Fujiwara S 《The Journal of biological chemistry》2011,286(17):14861-14869
We report that dermatopontin (DP), an abundant dermal extracellular matrix protein, is found in the fibrin clot and in the wound fluid, which comprise the provisional matrix at the initial stage of wound healing. DP was also found in the serum but at a lower concentration than that in wound fluid. DP co-localized with both fibrin and fibronectin on fibrin fibers and interacted with both proteins. Both normal fibroblast and HT1080 cell adhesion to the fibrin-fibronectin matrix were dose-dependently enhanced by DP, and the adhesion was mediated by α5β1 integrin. The cytoskeleton was more organized in the cells that adhered to the fibrin-fibronectin-DP complex. When incubated with DP, fibronectin formed an insoluble complex of fibronectin fibrils as visualized by electron microscopy. The interacting sites of fibronectin with DP were the first, thirteenth, and fourteenth type III repeats (III(1), III(13), and III(14)), with III(13) and III(14) assumed to be the major sites. The interaction between III(2-3) and III(12-14) was inhibited by DP, whereas the interaction between I(1-5) and III(12-14) was specifically and strongly enhanced by DP. Because the interaction between III(2-3) and III(12-14) is involved in forming a globular conformation of fibronectin, and that between I(1-5) and III(12-14) is required for forming fibronectin fibrils, DP promotes fibronectin fibril formation probably by changing the fibronectin conformation. These results suggest that DP has an accelerating role in fibroblast cell adhesion to the provisional matrix in the initial stage of wound healing. 相似文献
195.
Kazushi Hanyu Ryoko T. Ichiki Satoshi Nakamura Yooichi Kainoh 《Applied Entomology and Zoology》2011,46(4):565-571
Odors from corn plants infested with the larvae of the noctuid herbivore Mythimna separata (Walker) attract tachinid fly, Exorista japonica Townsend, females; and odors from corn plants artificially damaged also attract this fly. We investigated the responses of
flies to herbivore-infested, artificially damaged, and undamaged plants before and after arrival at the target plants to measure
timing of the behavioral sequence. The behavior of the flies for 10 min after takeoff from a release point was observed in
a wind-tunnel bioassay. The percentage of flies attracted to the plants was higher in infested and artificially damaged plants
than in undamaged plants. Latency before takeoff was longer in undamaged plants, and time from takeoff to arrival at the plant
was also longer in undamaged plants. Moreover, flies stayed longer on infested and artificially damaged plants. Flies walked
longer on infested plants than on artificially damaged and undamaged plants. In this paper, we summarize the behavioral data
and discuss the host-searching behavior of E. japonica females. 相似文献
196.
Tetsuji Itoh Yoshikazu Sato Hifumi Tsuruga Tsutomu Mano Masao Kohira Masami Yamanaka Shinsuke Kasai Kyoko Kobayashi Ryûtarô Iwata 《Acta theriologica》2013,58(2):127-138
Estimating the genetic structure of a population is important for the conservation and management of wildlife. In the present study, our aim was to estimate the genetic structure of the brown bear (Ursus arctos) population in eastern Hokkaido by performing a Bayesian clustering analysis. To accomplish this goal, we used 15 microsatellites to generate genotypic data from tissue samples collected from 646 bears between 1996 and 2008. Using this genotypic data and the geographic locations where the bears were captured, GENELAND analysis detected six subpopulations. Based on the genotypic data, the STRUCTURE analysis revealed three subpopulations. As inferred from the GENELAND analysis, the core zones of the subpopulations (G-a through G-f) were located in the Shiranuka Hills (G-a), the northern area of the Shiranuka Hills (G-b), the eastern slope of the Daisetsuzan Mountains (G-c), the northern slope of the Akan Mountain Range (G-d), the Shiretoko Peninsula (G-e), and Akkeshi District (G-f). The STRUCTURE analysis indicated that G-b and G-d were influenced by gene flow from other subpopulations. National routes, towns, and farm fields were considered to have formed the distribution boundaries among the subpopulations. A high level of genetic differentiation was not observed among the six subpopulations, with the exception of G-f (F st?=?1.35–0.176, D s?=?0.246–0.349), which showed a geographically discontinuous distribution. We suggest that the loss of forest areas through future regional development and road building should be avoided to facilitate gene flow in brown bears in Hokkaido. 相似文献
197.
Yuki Ohsaki Jinglei Cheng Kazushi Yamairi Xiaoyue Pan M. Mahmood Hussain Toyoshi Fujimoto 《FEBS letters》2013
ApoB-crescent, an endoplasmic reticulum (ER)-lipid droplet amalgamation structure, is a useful marker to indicate aberrant lipidated apolipoprotein B accumulation in the hepatocyte ER. Blockade of the ER-to-Golgi transport by either vesicle transport inhibitors or dominant-negative Arf1 caused a significant increase in ApoB-crescents. However, a low concentration of Brefeldin A induced the same result without affecting protein secretion, suggesting ADP-ribosylation as an additional mechanism. ADP-ribosylation inhibitors not only suppressed the increase of ApoB-crescents, but also rapidly dissolved existing ApoB-crescents. These results implicate the involvement of ADP-ribosylation in the ApoB-crescent formation and maintenance process at the ER. 相似文献
198.
Elizabeth A. Fry Pankaj Taneja Dejan Maglic Sinan Zhu Guangchao Sui Kazushi Inoue 《PloS one》2013,8(10)
Our recent study shows a pivotal role of Dmp1 in quenching hyperproliferative signals from HER2 to the Arf-p53 pathway as a safety mechanism to prevent breast carcinogenesis. To directly demonstrate the role of Dmp1 in preventing HER2/neu-driven oncogenic transformation, we established Flag-Dmp1α transgenic mice (MDTG) under the control of the mouse mammary tumor virus (MMTV) promoter. The mice were viable but exhibited poorly developed mammary glands with markedly reduced milk production; thus more than half of parous females were unable to support the lives of new born pups. The mammary glands of the MDTG mice had very low Ki-67 expression but high levels of Arf, Ink4a, p53, and p21Cip1, markers of senescence and accelerated aging. In all strains of generated MDTG;neu mice, tumor development was significantly delayed with decreased tumor weight. Tumors from MDTG;neu mice expressed Flag-Dmp1α and Ki-67 in a mutually exclusive fashion indicating that transgenic Dmp1α prevented tumor growth in vivo. Genomic DNA analyses showed that the Dmp1α transgene was partially lost in half of the MDTG;neu tumors, and Western blot analyses showed Dmp1α protein downregulation in 80% of the cases. Our data demonstrate critical roles of Dmp1 in preventing mammary tumorigenesis and raise the possibility of treating breast cancer by restoring Dmp1α expression. 相似文献
199.
Pei-Yu Chu Yu-Chang Tyan Yao-Shen Chen Hsiu-Lin Chen Po-Liang Lu Yu-Hsien Chen Bao-Chen Chen Tsi-Shu Huang Chu-Feng Wang Hui-Ju Su Yong-Ying Shi Bintou Sanno-Duanda Kuei-Hsiang Lin Kazushi Motomura 《PloS one》2015,10(6)
The infectious activity of coxsackievirus B1 (CV-B1) in Taiwan was high from 2008 to 2010, following an alarming increase in severe neonate disease in the United States (US). To examine the relationship between CV-B1 strains isolated in Taiwan and those from other parts of the world, we performed a phylodynamic study using VP1 and partial 3Dpol (414 nt) sequences from 22 strains of CV-B1 isolated in Taiwan (1989–2010) and compared them to sequences from strains isolated worldwide. Phylogenetic trees were constructed by neighbor-joining, maximum likelihood, and Bayesian Monte Carlo Markov Chain methods. Four genotypes (GI–IV) in the VP1 region of CV-B1 and three genotypes (GA–C) in the 3Dpol region of enterovirus B were identified and had high support values. The phylogenetic analysis indicates that the GI and GIII strains in VP1 were geographically distributed in Taiwan (1993–1994) and in India (2007–2009). On the other hand, the GII and GIV strains appear to have a wider spatiotemporal distribution and ladder-like topology A stair-like phylogeny was observed in the VP1 region indicating that the phylogeny of the virus may be affected by different selection pressures in the specified regions. Further, most of the GI and GII strains in the VP1 tree were clustered together in GA in the 3D tree, while the GIV strains diverged into GB and GC. Taken together, these data provide important insights into the population dynamics of CV-B1 and indicate that incongruencies in specific gene regions may contribute to spatiotemporal patterns of epidemicity for this virus. 相似文献
200.
Kazushi Yamane Fumiharu Kimura Kiichi Unoda Takafumi Hosokawa Takahiko Hirose Hiroki Tani Yoshimitsu Doi Simon Ishida Hideto Nakajima Toshiaki Hanafusa 《PloS one》2013,8(7)