全文获取类型
收费全文 | 392篇 |
免费 | 29篇 |
专业分类
421篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2019年 | 2篇 |
2018年 | 5篇 |
2017年 | 2篇 |
2016年 | 7篇 |
2015年 | 16篇 |
2014年 | 22篇 |
2013年 | 24篇 |
2012年 | 36篇 |
2011年 | 34篇 |
2010年 | 16篇 |
2009年 | 10篇 |
2008年 | 31篇 |
2007年 | 35篇 |
2006年 | 34篇 |
2005年 | 27篇 |
2004年 | 25篇 |
2003年 | 17篇 |
2002年 | 25篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 4篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有421条查询结果,搜索用时 0 毫秒
61.
Onodera H Kaneko M Takahashi Y Uochi Y Funahashi J Nakashima T Soga S Suzuki M Ikeda S Yamashita Y Rahayu ES Kanda Y Ichimura M 《Bioorganic & medicinal chemistry letters》2008,18(5):1588-1591
Hsp90 is an attractive chemotherapeutic target because it is essential to maturation of multiple oncogenes. We describe the conformational significance of EH21A1-A4, phenolic derivatives of geldanamycin isolated from Streptomyces sp. Their native free structures are similar to the active form of geldanamycin bound to Hsp90 protein. Their conformational character is a probable reason for their high-affinity binding. Lack of toxic benzoquinone in EH21A1-A4 also adds to their potential as lead compounds for anti-tumor drugs. 相似文献
62.
Saito S Yano K Sharma S McMahon HE Shimasaki S 《Protein science : a publication of the Protein Society》2008,17(2):362-370
Bone morphogenetic protein-15 (BMP-15) is an oocyte-secreted factor critical for the regulation of ovarian physiology. When recombinant human BMP-15 (rhBMP-15) produced in human embryonic kidney 293 cells was subjected to SDS-PAGE analysis, two mature protein forms corresponding to 16 kDa (P16) and 17 kDa (P17) were observed. Despite the physiological relevance and critical function of BMP-15 in female reproduction, little is known about the structure of rhBMP-15. Here, we have analyzed the structure of the rhBMP-15 mature proteins (P16 and P17) using state-of-the-art proteomics technology. Our findings are as follows: (1) the N-terminal amino acid of P16 and P17 is pyroglutamic acid; (2) the Ser residue at the sixth position of P16 is phosphorylated; (3) P17 is O-glycosylated at Thr10; and (4) the C-terminal amino acid of P16 and P17 is truncated. These findings are the first knowledge of the structure of rhBMP-15 mature protein toward understanding the molecular basis of BMP-15 function and could provide an important contribution to the rapidly progressing research area involving oocyte-specific growth factors in modulation of female fertility. 相似文献
63.
Kazuhiko Shimizu Shunichi Morikawa Shuji Kitahara Taichi Ezaki 《Cell and tissue research》2009,338(3):423-432
Although the immunological and hemodynamical significance of the spleen is of great importance, few reports detail the lymphatic
vessels in this organ. We have used an immunohistochemical three-dimensional imaging technique to characterize lymphatic vessels
in the normal mouse spleen and have successfully demonstrated their spatial relationship to the blood vascular system for
the first time. Lymphatic markers, such as LYVE-1, VEGFR-3, and podoplanin, show different staining patterns depending on
their location in the spleen. LYVE-1-positive lymphatic vessels run reverse to the arterial blood flow along the central arteries
in the white pulp and trabecular arteries and exit the spleen from the hilum. These lymphatic vessels are surrounded by type
IV collagen, indicating that they are collecting lymphatic vessels rather than lymphatic capillaries. Podoplanin is expressed
not only in lymphatic vessels, but also in stromal cells in the white pulp. These podoplanin-positive cells form fine meshworks
surrounding the lymphatic vessels and central arteries. Following intravenous transplantation of lymphocytes positive for
green fluorescent protein (GFP+) into normal recipient mice, donor cells appear in the meshworks within 1 h and accumulate in the lymphatic vessels within
6 h after injection. The GFP+ cells further accumulate in a draining celiac lymph node through the efferent lymphatic vessels from the hilum. These meshworks
might therefore act as an extravascular lymphatic pathway and, together with ordinary lymphatic vessels, play a primary role
in the cell traffic of the spleen, additional to the blood circulatory system. 相似文献
64.
Moderate alcohol consumption is associated with better endothelial function: a cross sectional study
Keiko Suzuki Mitchell SV Elkind Bernadette Boden-Albala Zhezhen Jin Grace Berry Marco R Di Tullio Ralph L Sacco Shunichi Homma 《BMC cardiovascular disorders》2009,9(1):1-5
Background
Natural heterologous valved conduits with a diameter greater than 22 mm that can be used for right ventricular outflow tract reconstruction in adults are not commercially available. The purpose of this study was to measure by ultrasonography the maximum diameter of the distended jugular veins of horses and cattle, respectively, to identify a population of animals that would be suitable for post-mortem collection of jugular veins at sizes greater than 22 mm.Methods
The study population included 60 Warmblood horses, 25 Freiberger horses, 20 Brown Swiss cows, and 20 Holstein cows (including 10 Holstein and 10 Red Holstein). The maximum cross-sectional diameter of the distended jugular veins was measured at a location half-way between the mandibular angle and the thoracic inlet. The thoracic circumference (heart girth length) was used as a surrogate of body size. The jugular vein diameters of the different populations were compared by analysis of variance and the association between heart girth length and jugular vein diameter was determined in each of the four study populations by linear regression analysis.Results
There was considerable individual variation of jugular vein diameters within each of the four study populations. There was no statistically significant relationship between thoracic circumference and jugular vein diameter in any of the populations. The jugular vein diameters of Brown Swiss cows were significantly larger than those of any of the other populations. Warmblood horses had significantly larger jugular vein diameters compared to Freiberger horses.Conclusion
The results of this study suggest that the production of bovine or equine xenografts with diameters of greater than 22 mm would be feasible. Differences between species and breeds need to be considered. However, prediction of the jugular vein diameter based on breed and heart girth length in an individual animal is inaccurate. 相似文献65.
Jun Suzuki Katsumi Yamaguchi Masaki Kajikawa Kenji Ichiyanagi Noritaka Adachi Hideki Koyama Shunichi Takeda Norihiro Okada 《PLoS genetics》2009,5(4)
Long interspersed elements (LINEs) are transposable elements that proliferate within eukaryotic genomes, having a large impact on eukaryotic genome evolution. LINEs mobilize via a process called retrotransposition. Although the role of the LINE-encoded protein(s) in retrotransposition has been extensively investigated, the participation of host-encoded factors in retrotransposition remains unclear. To address this issue, we examined retrotransposition frequencies of two structurally different LINEs—zebrafish ZfL2-2 and human L1—in knockout chicken DT40 cell lines deficient in genes involved in the non-homologous end-joining (NHEJ) repair of DNA and in human HeLa cells treated with a drug that inhibits NHEJ. Deficiencies of NHEJ proteins decreased retrotransposition frequencies of both LINEs in these cells, suggesting that NHEJ is involved in LINE retrotransposition. More precise characterization of ZfL2-2 insertions in DT40 cells permitted us to consider the possibility of dual roles for NHEJ in LINE retrotransposition, namely to ensure efficient integration of LINEs and to restrict their full-length formation. 相似文献
66.
67.
Kobashigawa S Suzuki K Yamashita S 《Biochemical and biophysical research communications》2011,414(4):795-800
Ionizing radiation is known to increase intracellular level of reactive oxygen species (ROS) through mitochondrial dysfunction. Although it has been as a basis of radiation-induced genetic instability, the mechanism involving mitochondrial dysfunction remains unclear. Here we studied the dynamics of mitochondrial structure in normal human fibroblast like cells exposed to ionizing radiation. Delayed mitochondrial production was peaked 3 days after irradiation, which was coupled with accelerated mitochondrial fission. We found that radiation exposure accumulated dynamin-related protein 1 (Drp1) to mitochondria. Knocking down of Drp1 expression prevented radiation induced acceleration of mitochondrial fission. Furthermore, knockdown of Drp1 significantly suppressed delayed production of mitochondrial . Since the loss of mitochondrial membrane potential, which was induced by radiation was prevented in cells knocking down of Drp1 expression, indicating that the excessive mitochondrial fission was involved in delayed mitochondrial dysfunction after irradiation. 相似文献
68.
Advanced glycation end products (AGEs) and their receptor (RAGE) have been shown to play a role in insulin resistance. We have previously shown that combination therapy with nateglinide (NAT) and telmisartan (TEL) improves postprandial metabolic derangements in Zucker fatty (ZF) rats, an animal model of insulin resistance with obesity. However, effects of combination therapy on insulin resistance remain unknown. We investigated here whether combination therapy with TEL and NAT could ameliorate insulin resistance in ZF rats by suppressing AGE-RAGE axis. NAT and/or TEL inhibited insulin receptor substrate-1 (IRS-1) serine phosphorylations at 307 and 636/639 residues in the liver of ZF rats. Further, combination therapy with NAT and TEL, but not each monotherapy alone, significantly restored the decrease in hepatic IRS-1 tyrosine phosphorylation in these animals. In addition, serum levels of AGEs, RAGE expression levels in the liver and hepatic AGE-RAGE index were decreased in NAT plus TEL-treated ZF rats. The present study suggests that combination therapy with NAT and TEL could ameliorate insulin resistance in ZF rats by suppressing the AGE-RAGE axis in the liver. 相似文献
69.
Asada S Kuroda M Aoyagi Y Fukaya Y Tanaka S Konno S Tanio M Aso M Satoh K Okamoto Y Nakayama T Saito Y Bujo H 《American journal of physiology. Cell physiology》2011,301(1):C181-C185
Adipose tissue is expected to provide a source of proliferative cells for regenerative medicine and cell-transplantation therapies using gene transfer manipulation. We have recently identified ceiling culture-derived proliferative adipocytes (ccdPAs) from the mature adipocyte fraction as cells suitable as a therapeutic gene vehicle because of their stable proliferative capacity. In this study, we examined the capability of adipogenic differentiation of the ccdPAs compared with stromal vascular fraction (SVF)-derived progenitor cells (adipose-derived stem cells, ASCs) with regard to their multipotential ability to be converted to another lineage and therefore their potential to be used for regenerative medicine research. After in vitro passaging, the surface antigen profile and the basal levels of adipogenic marker genes of the ccdPAs were not obviously different from those of the ASCs. However, the ccdPAs showed increased lipid-droplet accumulation accompanied with higher adipogenic marker gene expression after stimulation of differentiation compared with the ASCs. The higher adipogenic potential of the ccdPAs than the ASCs from the SVF was maintained for 42 days in culture. Furthermore, the difference in the adipogenic response was enhanced after partial stimulation without indomethacin. These results indicate that the ccdPAs retain a high adipogenic potential even after in vitro passaging, thus suggesting the commitment of ccdPAs to stable mature adipocytes after autotransplantation, indicating that they may have potential for use in regenerative and gene-manipulated medicine. 相似文献
70.
Kenji Fujiwara Kenoki Ohuchida Masafumi Sada Kohei Horioka Charles D. Ulrich III Koji Shindo Takao Ohtsuka Shunichi Takahata Kazuhiro Mizumoto Yoshinao Oda Masao Tanaka 《PloS one》2014,9(9)