全文获取类型
收费全文 | 1186篇 |
免费 | 73篇 |
出版年
2023年 | 7篇 |
2022年 | 10篇 |
2021年 | 9篇 |
2020年 | 9篇 |
2019年 | 18篇 |
2018年 | 14篇 |
2017年 | 17篇 |
2016年 | 25篇 |
2015年 | 38篇 |
2014年 | 46篇 |
2013年 | 93篇 |
2012年 | 67篇 |
2011年 | 72篇 |
2010年 | 55篇 |
2009年 | 39篇 |
2008年 | 66篇 |
2007年 | 64篇 |
2006年 | 51篇 |
2005年 | 63篇 |
2004年 | 55篇 |
2003年 | 66篇 |
2002年 | 86篇 |
2001年 | 21篇 |
2000年 | 23篇 |
1999年 | 15篇 |
1998年 | 19篇 |
1997年 | 23篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 16篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 9篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 3篇 |
1985年 | 19篇 |
1983年 | 10篇 |
1982年 | 8篇 |
1980年 | 5篇 |
1975年 | 3篇 |
1972年 | 3篇 |
1969年 | 3篇 |
1968年 | 2篇 |
1967年 | 3篇 |
1966年 | 4篇 |
1965年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有1259条查询结果,搜索用时 15 毫秒
41.
Tomizo Niwa Sigeharu Inouye Takashi Tsuruoka Yoshihisa Koaze Taro Niida 《Bioscience, biotechnology, and biochemistry》2013,77(6):966-968
Glucose-6-phosphate dehydrogenase in a yeast, Hansenula mrakii IFO 0895 is induced when the cells are cultured in a medium containing lipid hydroperoxide. The enzyme was purified from H. mrakii to the homogeneous state on polyacrylamide gel electrophoresis. The molecular weight of the purified enzyme was estimated to be approximately 52kDa by SDS-PAGE and 130 kDa by Sephadex G-150column chromatography, respectively. The enzyme was specific to glucose-6-phosphate and NADP+, and Kmvalues for glucose-6-phosphate and NADP+ were 293µM and 24.1 µM, respectively. The enzyme activity was inhibited by diethylpyrocarbonate and 2, 4, 6-trinitrobenzene sulfonate, and by metal ions such as Zn2 +, Cd2 +, Cu2 +, and Al3 + . tert-Butyl hydroperoxide, a kind of lipid hydroperoxide, slightly(approximately 20%) increased the enzyme activity. 相似文献
42.
Yoshihisa Koaze Hitoshi Goi Kazumi Ezawa Yujiro Yamada Takeshi Hara 《Bioscience, biotechnology, and biochemistry》2013,77(4):216-223
Two kinds of proteolytic enzyme, tentatively named acid protease A and B which showed a single peak on electrophoresis individually, were isolated from the crude enzyme powder obtained from the broth filtrate cultured with Asper gillus niger var. macrosporus. Acid protease B is similar too the fungal acid protease previously reported, bccause the enzyme exhibits optimum activity on milk casein at about pH 2.6 and 55°C when the incubation was done at pH 2.6. Acid protease A is a new proteolytic enzyme, because the enzyme exhibits optimum activity on milk casein at about 2.0 and 70°C or 60°C when the incubation was done at pH 2.6 or 1.5 respectively. 相似文献
43.
Yoshihisa Tanaka Masanobu Kirita Yuko Abe Satoshi Miyata Motoyuki Tagashira Tomomasa Kanda 《Bioscience, biotechnology, and biochemistry》2013,77(7):1140-1146
Seven new O-methylated theaflavins (TFs) were synthesized by using O-methyltransferase from an edible mushroom. Using TFs and O-methylated TFs, metabolic stability in pooled human liver S9 fractions and inhibitory effect on H2O2-induced oxidative damage in human HepG2 cells were investigated. In O-methylation of theaflavin 3′-O-gallate (TF3′G), metabolic stability was potentiated by an increase in the number of introduced methyl groups. O-methylation of TF3,3′G did not affect metabolic stability, which was likely because of a remaining 3-O-galloyl group. The inhibitory effect on oxidative damage was assessed by measuring the viability of H2O2-damaged HepG2 cells treated with TFs and O-methylated TFs. TF3,3′G and O-methylated TFs increased cell viabilities significantly compared with DMSO, which was the compound vehicle (p?<?0.05), and improved to approximately 100%. Only TF3′G did not significantly increase cell viability. It was suggested that the inhibitory effect on H2O2-induced oxidative damage was potentiated by O-methylation or O-galloylation of TFs. 相似文献
44.
45.
46.
Yukiko Tomioka Yoshikazu Fujimoto Kanji Nakai Kinuyo Ozaki Sayo Yamamoto Haruka Suyama Masami Morimatsu Toshihiro Ito Etsuro Ono 《Biochemistry and Biophysics Reports》2016
Transgenic mouse lines expressing a soluble form of human nectin-2 (hNectin-2Ig Tg) exhibited distinctive elevation of amylase and lipase levels in the sera. In this study, we aimed to clarify the histopathology and to propose the transgenic mouse lines as new animal model for characteristic pancreatic exocrine defects. The significant increase of amylase and lipase levels in sera of the transgenic lines approximately peaked at 8 weeks old and thereafter, plateaued or gradually decreased. The histopathology in transgenic acinar cells was characterized by intracytoplasmic accumulation of abnormal proteins with decrease of normal zymogen granules. The hNectin-2Ig expression was observed in the cytoplasm of pancreatic acinar cells, which was consistent with zymogen granules. However, signals of hNectin-2Ig were very weak in the transgenic acinar cells with the abnormal cytoplasmic accumulaion. The PCNA-positive cells increased in the transgenic pancreas, which suggested the affected acinar cells were regenerated. Acinar cells of hNectin-2Ig Tg had markedly small number of zymogen granules with remarkable dilation of the endoplasmic reticulum (ER) lumen containing abundant abnormal proteins. In conclusion, hNectin-2Ig Tg is proposed as a new animal model for characteristic pancreatic exocrine defects, which are due to the ER stress induced by expression of mutated cell adhesion molecule that is a soluble form of human nectin-2. 相似文献
47.
Yoshihisa Shimizu Chiaki Yoshikawa Junji Suzuki Jun Qiu Edith van den Bosch 《Biotechnology letters》2016,38(3):403-408
Objective
When polymer brushes are applied as the inner coating for artificial blood vessels, they may induce unwanted responses in vascular endothelial cells continuously exposed to the polymer surface. Accordingly, we have examined the in vitro effect of non-biofouling concentrated polymer brushes (CPBs) on pro-inflammatory and angiogenic responses of human umbilical vein endothelial cells (HUVECs).Results
Micro-patterned CPBs were prepared on silicon wafers using biocompatible polymers, poly(poly(ethylene glycol)methyl ether methacrylate) (PPEGMA) and poly(2-hydroxyethyl methacrylate) (PHEMA). HUVECs were cultured on PPEGMA-CPBs and PHEMA-CPBs with different channel widths (20, 50, and 80 µm) and analyzed for mRNA expression of the pro-inflammatory cytokines IL-6 and IL-8 and angiogeneic vascular endothelial growth factor (VEGF). Irrespective of channel width, PHEMA-CPBs reduced the expression of all target genes, whereas PPEGMA-CPBs reduced VEGF and did not affect IL-6 and IL-8 levels.Conclusion
Micro-patterned CPBs, irrespective of chemical structure or adhesion area, do not induce the expression of important pro-inflammatory and angiogenic mediators in endothelial cells.48.
Genyan Liu Huaguang Li Jiaying Shi Wenjie Wang Kenjiro Furuta Di Liu Chunqing Zhao Fumiyo Ozoe Xiulian Ju Yoshihisa Ozoe 《Bioorganic & medicinal chemistry》2019,27(2):416-424
Competitive antagonists (CAs) of ionotropic GABA receptors (GABARs) reportedly exhibit insecticidal activity and have potential for development as novel insecticides for overcoming emerging resistance to traditional GABAR-targeting insecticides. Our previous studies demonstrated that 4,5-disubstituted 3-isoxazolols or 3-isothiazolols are an important class of insect GABAR CAs. In the present study, we synthesized a series of 4-aryl-5-carbamoyl-3-isoxazolols and examined their antagonism of insect GABARs expressed in Xenopus oocytes. Several of these 3-isoxazolols exhibited potent antagonistic activities against housefly and common cutworm GABARs, with IC50 values in the low-micromolar range in both receptors. 4-(3-Amino-4-methylphenyl)-5-carbamoyl-3-isoxazolol (3u) displayed the highest antagonism, with IC50 values of 2.0 and 0.9?μM in housefly and common cutworm GABARs, respectively. Most of the synthesized 3-isoxazolols showed moderate larvicidal activities against common cutworms, with more than 50% mortality at 100?μg/g. These results indicate that 4-monocyclic aryl-5-carbamoyl-3-isoxazolol is a promising scaffold for insect GABAR CA discovery and provide important information for the design and development of GABAR-targeting insecticides with a novel mode of action. 相似文献
49.
Kumi Morikawa Kazuomi Nakamura Yoshiko Suyama Kenshiro Yamamoto Kohei Fukuoka Shunjiro Yagi Yasuaki Shirayoshi Tetsuya Ohbayashi Ichiro Hisatome 《Biochemistry and Biophysics Reports》2019
In the present study, we have established a novel transgenic mouse and transgenic rats with dual reporters of EGFP and ELuc. In these transgenic (Tg) rodents, both GFP fluorescent and luciferase luminescent signals were ubiquitously detected in the heart, liver, kidney and testis, while only the GFP signal was detected in the brain. This expression system is based on a P2A linked EGFP/ELuc protein allowing both signals to be generated simultaneously. Microscopy experiments, FCM, and luciferase assays showed strong expression in freshly isolated ADSCs from Tg rodents upon transplantation of Tg rat-derived ADSCs into wild-type-mice. The ELuc transgene signal was observed and traced in vivo, and EGFP positive cells could be recovered from ELuc positive tissues in engraftment sites of wild-type mice for multiple analysis. These dual reporter Tg rodents are a useful reconstituted model system of regenerative medicine and are a valuable tool to study stem cells. 相似文献
50.
Zhang J Schulze KL Hiesinger PR Suyama K Wang S Fish M Acar M Hoskins RA Bellen HJ Scott MP 《Genetics》2007,176(2):1307-1322
Rab proteins are small GTPases that play important roles in transport of vesicle cargo and recruitment, association of motor and other proteins with vesicles, and docking and fusion of vesicles at defined locations. In vertebrates, >75 Rab genes have been identified, some of which have been intensively studied for their roles in endosome and synaptic vesicle trafficking. Recent studies of the functions of certain Rab proteins have revealed specific roles in mediating developmental signal transduction. We have begun a systematic genetic study of the 33 Rab genes in Drosophila. Most of the fly proteins are clearly related to specific vertebrate proteins. We report here the creation of a set of transgenic fly lines that allow spatially and temporally regulated expression of Drosophila Rab proteins. We generated fluorescent protein-tagged wild-type, dominant-negative, and constitutively active forms of 31 Drosophila Rab proteins. We describe Drosophila Rab expression patterns during embryogenesis, the subcellular localization of some Rab proteins, and comparisons of the localization of wild-type, dominant-negative, and constitutively active forms of selected Rab proteins. The high evolutionary conservation and low redundancy of Drosophila Rab proteins make these transgenic lines a useful tool kit for investigating Rab functions in vivo. 相似文献