全文获取类型
收费全文 | 161篇 |
免费 | 22篇 |
出版年
2023年 | 2篇 |
2021年 | 1篇 |
2020年 | 7篇 |
2019年 | 3篇 |
2018年 | 4篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 9篇 |
2014年 | 9篇 |
2013年 | 8篇 |
2012年 | 6篇 |
2011年 | 16篇 |
2010年 | 9篇 |
2009年 | 5篇 |
2008年 | 16篇 |
2007年 | 12篇 |
2006年 | 13篇 |
2005年 | 12篇 |
2004年 | 10篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1988年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1980年 | 1篇 |
排序方式: 共有183条查询结果,搜索用时 15 毫秒
91.
Nagamine T Takagi H Takayama H Kojima A Kakizaki S Mori M Nakajima K 《Biological trace element research》2000,75(1-3):53-63
We have evaluated the efficacy of interferon-α (IFN-α) plus zinc therapy in hepatitis C patients with genotype 1b, poor responders
for IFN alone. Ten patients were injected with 10 MU of IFN-α every day for 4 wk, followed by three times a week for 20 wk
(control group). Nine patients took 300 mg of zinc sulfate a day orally during IFN-α therapy (zinc sulfate group), and 15
patients took IFN-α and 150 mg of polaprezinc (polaprezinc group).
On the d 8 of IFN therapy, circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the
zinc sulfate group or control group. Serum ALT levels normalized in 73.3% of the polaprezinc group, 55.6% of the zinc sulfate
group, and 40.0% of the control group at 6 mo after the end of IFN therapy. Sustained eradication for the hepatitis C virus
RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group (53.3%
vs 11.1%, p<0.05) or the control group (20.0%). No clinical side effects of zinc were observed at the dose used. The data suggest that
polaprezinc is expected to increase the therapeutic response of IFN-α for chronic hepatitis C with genotype 1b. 相似文献
92.
Kakizaki S Takagi H Ichikawa T Abe T Yamada T Suzuki K Kojima A Takayama H Takezawa J Nagamine T Mori M 《Biological trace element research》2000,73(2):151-162
We examined the efficacy of interferon (IFN) therapy for chronic hepatitis C (CHC) in view of the change of liver histology
and iron staining before and after IFN therapy.
Enrolled in this study were 109 patients with CHC who completed IFN treatment and were followed for at least 1 yr after the
end of IFN therapy. Serum iron, unsaturated-iron-binding capacity (UIBC), and total-iron-binding capacity (TIBC) were assessed
before IFN therapy. Knodell’s histological activity index (HAI) score and iron staining were examined in 55 patients in whom
liver biopsy was performed at two points: before and 1 yr after IFN therapy. Serum iron levels before IFN therapy did not
correlate with the response to IFN. The HAI score significantly decreased after IFN therapy in complete responders (p<0.01) and biochemical responders (p<0.01). Three factors in the HAI, periportal necrosis, intralobular necrosis, and portal inflammation, but not fibrosis, were
significantly decreased in complete responders (p<0.01) and biochemical responders (p<0.01). Of 55 patients, 23 (41.8%) were positive for iron staining before IFN therapy and 14 of 55 (25.5%) after IFN therapy.
The positive rate for iron staining tended to decrease after IFN therapy, not correlating to the response to IFN, but the
change was not statistically significant.
In conclusion, the histological improvement by IFN therapy was mostly seen in necroinflammatory changes but not in fibrosis
at least 1 yr after IFN, and iron staining tended to decrease after IFN therapy. 相似文献
93.
94.
An introduced population of Chorda asiatica (Chordaceae,Laminariales) in Puget Sound,Pacific coast of North America 下载免费PDF全文
Hiroshi Kawai Takeaki Hanyuda Thomas Mumford J. Robert Waaland 《Phycological Research》2015,63(2):154-158
Northeastern Pacific Ocean and northwestern Atlantic Ocean populations of Chorda species, which have not been examined in previous phylogenetic studies, were investigated. All specimens that were collected in Hood Canal, Puget Sound, WA, USA, Pacific coast of North America, showed identical ITS‐5.8S rDNA sequences, and they were included in the clade of Japanese Chorda asiatica. With morphological data added to the molecular data, they were identified as C. asiatica and were concluded to be non‐indigenous populations, most likely introduced with oyster spat together with Sargassum muticum. Specimens collected in New York, NY, USA, Atlantic coast of North America, were genetically closest to C. filum from Newfoundland and were identified as C. filum. The genetic divergence of the North Atlantic populations of C. filum was relatively small compared to that of Japanese C. asiatica considering their broader distributional ranges on both sides of the Atlantic. 相似文献
95.
Nakano-Kobayashi A Yamazaki M Unoki T Hongu T Murata C Taguchi R Katada T Frohman MA Yokozeki T Kanaho Y 《The EMBO journal》2007,26(4):1105-1116
Synaptic vesicles (SVs) are retrieved by clathrin-mediated endocytosis at the nerve terminals. Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] drives this event by recruiting the components of the endocytic machinery. However, the molecular mechanisms that result in local generation of PI(4,5)P2 remain unclear. We demonstrate here that AP-2 complex directly interacts with phosphatidylinositol 4-phosphate 5-kinase gamma661 (PIP5Kgamma661), the major PI(4,5)P2-producing enzyme in the brain. The beta2 subunit of AP-2 was found to bind to the C-terminal tail of PIP5Kgamma661 and cause PIP5Kgamma661 activation. The interaction is regulated by PIP5Kgamma661 dephosphorylation, which is triggered by depolarization in mouse hippocampal neurons. Finally, overexpression of the PIP5Kgamma661 C-terminal region in hippocampal neurons suppresses depolarization-dependent SV endocytosis. These findings provide evidence for the molecular mechanism through which PIP5Kgamma661 locally generates PI(4,5)P2 in hippocampal neurons and suggest a model in which the interaction trigger SV endocytosis. 相似文献
96.
Multimodal and multiplex spectral imaging of rat cornea ex vivo using a white‐light laser source 下载免费PDF全文
Hiroki Segawa Yuichi Kaji Philippe Leproux Vincent Couderc Takeaki Ozawa Tetsuro Oshika Hideaki Kano 《Journal of biophotonics》2015,8(9):705-713
We applied our multimodal nonlinear spectral imaging microscope to the measurement of rat cornea. We successfully obtained multiple nonlinear signals of coherent anti‐Stokes Raman scattering (CARS), third‐order sum frequency generation (TSFG), and second harmonic generation (SHG). Depending on the nonlinear optical processes, the cornea tissue was visualized with different image contrast mechanism simultaneously. Due to white‐light laser excitation, multiplex CARS and TSFG spectra were obtained. Combined multimodal and spectral analysis clearly elucidated the layered structure of rat cornea with molecular structural information. This study indicates that our multimodal nonlinear spectral microscope is a promising bioimaging method for tissue study.
97.
We developed genetically encoded RNA probes for characterizing localization and dynamics of mitochondrial RNA (mtRNA) in single living cells. The probes consist of two RNA-binding domains of PUMILIO1, each connected with split fragments of a fluorescent protein capable of reconstituting upon binding to a target RNA. We designed the probes to specifically recognize a 16-base sequence of mtRNA encoding NADH dehydrogenase subunit 6 (ND6) and to be targeted into the mitochondrial matrix, which allowed real-time imaging of ND6 mtRNA localization in living cells. We showed that ND6 mtRNA is localized within mitochondria and concentrated particularly on mitochondrial DNA (mtDNA). Movement of the ND6 mtRNA is restricted but oxidative stress induces the mtRNA to disperse in the mitochondria and gradually decompose. These probes provide a means to study spatial and temporal mRNA dynamics in intracellular compartments in living mammalian cells. 相似文献
98.
99.
Sayaka Akieda-Asai Nobuhiro Zaima Koji Ikegami Tomoaki Kahyo Ikuko Yao Takahiro Hatanaka Shun-ichiro Iemura Rika Sugiyama Takeaki Yokozeki Yoshinobu Eishi Morio Koike Kyoji Ikeda Takuya Chiba Haruyoshi Yamaza Isao Shimokawa Si-Young Song Akira Matsuno Akiko Mizutani Motoji Sawabe Moses V. Chao Masashi Tanaka Yasunori Kanaho Tohru Natsume Haruhiko Sugimura Yukari Date Michael W. McBurney Leonard Guarente Mitsutoshi Setou 《PloS one》2010,5(7)
Background
SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there.Methodology/Principal Findings
Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ and enhanced PIP5Kγ enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice.Conclusions/Significance
Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body. 相似文献100.