全文获取类型
收费全文 | 1650篇 |
免费 | 77篇 |
出版年
2022年 | 15篇 |
2021年 | 21篇 |
2020年 | 20篇 |
2019年 | 12篇 |
2018年 | 18篇 |
2017年 | 21篇 |
2016年 | 32篇 |
2015年 | 67篇 |
2014年 | 60篇 |
2013年 | 106篇 |
2012年 | 111篇 |
2011年 | 80篇 |
2010年 | 64篇 |
2009年 | 58篇 |
2008年 | 74篇 |
2007年 | 77篇 |
2006年 | 100篇 |
2005年 | 46篇 |
2004年 | 67篇 |
2003年 | 74篇 |
2002年 | 69篇 |
2001年 | 40篇 |
2000年 | 37篇 |
1999年 | 35篇 |
1998年 | 22篇 |
1997年 | 12篇 |
1996年 | 21篇 |
1995年 | 13篇 |
1994年 | 16篇 |
1993年 | 15篇 |
1992年 | 26篇 |
1991年 | 18篇 |
1990年 | 14篇 |
1989年 | 10篇 |
1988年 | 36篇 |
1987年 | 17篇 |
1986年 | 25篇 |
1985年 | 17篇 |
1984年 | 18篇 |
1982年 | 7篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1977年 | 7篇 |
1975年 | 10篇 |
1974年 | 15篇 |
1973年 | 15篇 |
1972年 | 20篇 |
1971年 | 13篇 |
1967年 | 6篇 |
排序方式: 共有1727条查询结果,搜索用时 140 毫秒
61.
The extracellular lipase from Candida paralipolytica required essential activators* (usually bile- or calcium salts) for the in vitro hydrolysis of triglycerides. The reaction systems emulsified with gum arabic, gelatin, lecithin, methyl cellulose, pectin, polyvinyl alcohol, sodium cholate, or without emulsifier were compared concerning requirement for essential activator, inhibition with sodium chloride and maximum reaction rate, and the following findings have been obtained. (1) The emulsions used can be classified into five groups by the essential activator requirement. (2) The inhibition with sodium chloride depended on reaction system. (3) Each reaction system gave a similar reaction rate at pH 8.2. (4) Long-chain fatty acid dissolved in substrate was necessary to the activation with calcium salts. 相似文献
62.
Yasuhide Ota Masaru Suzuki Koichi Yamada 《Bioscience, biotechnology, and biochemistry》2013,77(3):390-391
Properties of autolytic breakdown of rat skeletal muscle proteins in the alkaline pH range have been reported. The activity is almost exclusively localized in the myofibrillar fraction, but is not solubilized with Triton X-100. The activity is affected by the KCI concentration in the reaction mixture. In 0.6 M and the more concentrated KCI solutions, the maximum activity is attained. The optimum pH of the activity is in the range of pH 7.5~9.5, and the optimum temperature is between 47~57°C.This autolytic activity seems to be different from catheptic activity which shows its optimum pH in the acid pH range. Moreover, though more than half of the catheptic activity of rat skeletal muscle is recovered in the myofibrillar fraction, the catheptic activity in the myofibrillar fraction can be removed from the fraction by the extraction with dilute saline solution containing Triton X-100. 相似文献
63.
64.
Takayoshi Suzuki Yuki Kasuya Yukihiro Itoh Yosuke Ota Peng Zhan Kaori Asamitsu Hidehiko Nakagawa Takashi Okamoto Naoki Miyata 《PloS one》2013,8(7)
To find histone deacetylase 3 (HDAC3)-selective inhibitors, a series of 504 candidates was assembled using “click chemistry”, by reacting nine alkynes bearing a zinc-binding group with 56 azide building blocks in the presence of Cu(I) catalyst. Screening of the 504-member triazole library against HDAC3 and other HDAC isozymes led to the identification of potent and selective HDAC3 inhibitors T247 and T326. These compounds showed potent HDAC3 inhibition with submicromolar IC50s, whereas they did not strongly inhibit other isozymes. Compounds T247 and T326 also induced a dose-dependent selective increase of NF-κB acetylation in human colon cancer HCT116 cells, indicating selective inhibition of HDAC3 in the cells. In addition, these HDAC3-selective inhibitors induced growth inhibition of cancer cells, and activated HIV gene expression in latent HIV-infected cells. These findings indicate that HDAC3-selective inhibitors are promising candidates for anticancer drugs and antiviral agents. This work also suggests the usefulness of the click chemistry approach to find isozyme-selective HDAC inhibitors. 相似文献
65.
Ayako Kitano Takeo Shimasaki Yuri Chikano Mitsutoshi Nakada Mayumi Hirose Tomomi Higashi Yasuhito Ishigaki Yoshio Endo Takahisa Takino Hiroshi Sato Yoshimichi Sai Ken-ichi Miyamoto Yoshiharu Motoo Kazuyuki Kawakami Toshinari Minamoto 《PloS one》2013,8(2)
Background and Purpose
The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer.Methods
Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined.Results
Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts.Conclusion
The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer. 相似文献66.
Noriyasu Ota Satoko Soga Akira Shimotoyodome 《Bioscience, biotechnology, and biochemistry》2016,80(12):2412-2417
Our previous studies demonstrated that dietary supplementation with tea catechins combined with exercise improved endurance capacity in mice. This study aimed to demonstrate the effect of daily tea catechin consumption on aerobic capacity in humans. Sixteen Japanese non-athlete male subjects (aged 25–47 years) took 500 mL of a test beverage with or without tea catechins (570 mg) daily for 8 weeks and attended a training program twice a week. Aerobic capacity was evaluated by indirect calorimetry and near-infrared spectroscopy during graded cycle exercise. Catechin beverage consumption was associated with a significantly higher ventilation threshold during exercise and a higher recovery rate of oxygenated hemoglobin and myoglobin levels after graded cycle exercise when compared to subjects receiving the placebo beverage. These results indicate that daily consumption of tea catechins increases aerobic capacity when combined with semiweekly light exercise, which may be due to increased skeletal muscle aerobic capacity. 相似文献
67.
Dae-In Kim Il-Kook Park Jong-Sun Kim Hidetoshi Ota Woo-Jin Choi Il-Hun Kim 《Animal cells and systems.》2019,23(1):64-70
Differential microhabitat use may be beneficial to achieving fitness in seasonally variable environmental conditions. To explore whether the microhabitat use of the nocturnal Schlegel’s Japanese gecko, Gekko japonicus, varies seasonally and depends on juvenile, male, and female reproductive groups, we investigated five categorical and five quantitative measure variables of microhabitat use in a wild population both in spring and summer. Most geckos were found on white, vertical planes of concrete and plastered brick walls. None of the categorical variables (type of location, substrate, substrate color, light source, and refuge) significantly differed according to season or group, while substrate temperature and irradiance at the location where geckos were observed and the distance from the nearest potential refuge were significantly greater in summer than in spring. The quantitative measure variables did not differ among the reproductive groups. These results suggest that G. japonicus seasonally adjusts its microhabitat use mainly in terms of quantitative measure variables rather than categorical variables. 相似文献
68.
The effect of a serine protease (ASP) secreted from Aeromonas sobria on plasma coagulation was investigated. Proteolytically active ASP promoted human plasma coagulation in a dose-dependent manner. Consistent with the preference for a factor Xa-specific oligo-peptide substrate, ASP produced enzymatic activity from human prothrombin but not from factors IX and X. ASP cleaved prothrombin to produce enzymatically active 37 kDa-fragment displaying the same molecular mass as alpha-thrombin. ASP is the first bacterial serine protease that produces alpha-thrombin, through which ASP may contribute to the induction of thrombotic tendency in disseminated intravascular coagulation complicated with sepsis caused by A. sobria infections. 相似文献
69.
Murata T Lin MI Stan RV Bauer PM Yu J Sessa WC 《The Journal of biological chemistry》2007,282(22):16631-16643
Various cellular signals initiate calcium entry into cells, and there is evidence that lipid rafts and caveolae may concentrate proteins that regulate transmembrane calcium fluxes. Here, using mice deficient in caveolin-1 (Cav-1) and Cav-1 knock-out reconstituted with endothelium-specific Cav-1, we show that Cav-1 is essential for calcium entry in endothelial cells and governs the localization and protein-protein interactions between transient receptor channels C4 and C1. Thus, Cav-1 is required for calcium entry in vascular endothelial cells and perhaps other specialized cell types containing caveolae. 相似文献
70.