全文获取类型
收费全文 | 2464篇 |
免费 | 137篇 |
国内免费 | 2篇 |
出版年
2022年 | 10篇 |
2021年 | 31篇 |
2020年 | 11篇 |
2019年 | 20篇 |
2018年 | 61篇 |
2017年 | 25篇 |
2016年 | 39篇 |
2015年 | 76篇 |
2014年 | 90篇 |
2013年 | 150篇 |
2012年 | 163篇 |
2011年 | 145篇 |
2010年 | 119篇 |
2009年 | 110篇 |
2008年 | 149篇 |
2007年 | 182篇 |
2006年 | 172篇 |
2005年 | 135篇 |
2004年 | 147篇 |
2003年 | 127篇 |
2002年 | 165篇 |
2001年 | 25篇 |
2000年 | 34篇 |
1999年 | 33篇 |
1998年 | 40篇 |
1997年 | 28篇 |
1996年 | 26篇 |
1995年 | 16篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 22篇 |
1991年 | 19篇 |
1990年 | 11篇 |
1989年 | 20篇 |
1988年 | 18篇 |
1987年 | 17篇 |
1986年 | 6篇 |
1985年 | 12篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 13篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1971年 | 4篇 |
排序方式: 共有2603条查询结果,搜索用时 31 毫秒
71.
Keiji Saito Akira Nakao Tsuyoshi Shinozuka Kousei Shimada Satoshi Matsui Kiyoshi Oizumi Kazuki Yano Keiko Ohata Daisuke Nakai Yoko Nagai Satoru Naito 《Bioorganic & medicinal chemistry》2013,21(7):1628-1642
A cell-based assay was performed for the discovery of novel bone anabolic agents. Alkaline phosphatase (ALPase) activity of ST2 cells was utilized as an indicator of osteoblastic differentiation, and thienopyridine derivative 1 was identified as a hit compound. 3-Aminothieno[2,3-b]pyridine-2-carboxamide was confirmed to be a necessary core structure for the enhancement of ALPase activity, and then optimization of the C4-substituent on the thienopyridine ring was carried out. Introduction of cyclic amino groups to the C4-position of the thienopyridine ring improved the activity. Especially, N-phenyl-homopiperazine derivatives were found to be strong enhancers of ALPase among this new series. Furthermore, 3-amino-4-(4-phenyl-1,4-diazepan-1-yl)thieno[2,3-b]pyridine-2-carboxamide (15k) was orally administered to ovariectomized (OVX) rats over 6 weeks for evaluating the effects on areal bone mineral density (aBMD), and statistically significant improvements in aBMD were observed from the dosage of 10 mg/kg/day. 相似文献
72.
Masao Ohashi Takuji Oyama Endy Widya Putranto Tsuyoshi Waku Hiromi Nobusada Ken Kataoka Kenji Matsuno Masakazu Yashiro Kosuke Morikawa Nam-ho Huh Hiroyuki Miyachi 《Bioorganic & medicinal chemistry》2013,21(8):2319-2332
In the continuing study directed toward the development of peroxisome proliferator-activated receptor gamma (hPPARγ) agonist, we attempted to improve the water solubility of our previously developed hPPARγ-selective agonist 3, which is insufficiently soluble for practical use, by employing two strategies: introducing substituents to reduce its molecular planarity and decreasing its hydrophobicity via replacement of the adamantyl group with a heteroaromatic ring. The first approach proved ineffective, but the second was productive. Here, we report the design and synthesis of a series of α-benzyl phenylpropanoic acid-type hPPARγ partial agonists with improved aqueous solubility. Among them, we selected (R)-7j, which activates hPPARγ to the extent of about 65% of the maximum observed with a full agonist, for further evaluation. The ligand-binding mode and the reason for the partial-agonistic activity are discussed based on X-ray-determined structure of the complex of hPPARγ ligand-binding domain (LBD) and (R)-7j with previously reported ligand-LDB structures. Preliminal apoptotic effect of (R)-7j against human scirrhous gastric cancer cell line OCUM-2MD3 is also described. 相似文献
73.
Masaki Wakasugi Hiroaki Gouda Tomoyasu Hirose Akihiro Sugawara Tsuyoshi Yamamoto Kazuro Shiomi Toshiaki Sunazuka Satoshi Ōmura Shuichi Hirono 《Bioorganic & medicinal chemistry》2013,21(11):3214-3220
Human acidic mammalian chitinase (hAMCase) was recently shown to be involved in the development of asthma, suggesting a possible application for hAMCase inhibitors as novel therapeutic agents for asthma. We therefore initiated drug discovery research into hAMCase using a combination of in silico methodologies and a hAMCase assay system. We first selected 23 candidate hAMCase inhibitors from a database of four million compounds using a multistep screening system combining Tripos Topomer Search technology, a docking calculation and two-dimensional molecular similarity analysis. We then measured hAMCase inhibitory activity of the selected compounds and identified seven compounds with IC50 values ?100 μM. A model describing the binding modes of these hit compounds to hAMCase was constructed, and we discuss the structure–activity relationships of the compounds we identified, suggested by the model and the actual inhibitory activities of the compounds. 相似文献
74.
Tsuyoshi Fujitani 《Bioscience, biotechnology, and biochemistry》2013,77(11):762-766
It was found that the intercellular space of centrifuged sake yeast cultured in anaerobic medium is 0.263 ml/g, which is larger than that of bakers’ yeast. On the preparation of the calibration curve, this centrifuged sake yeast wras used as standard substance.The diameters of the majority of cells were included in a range of 3~8µ during the whole course of cultural development. A similar distribution was found on the cells cultured in an abnormal medium. From these results, clearly, the turbidimetric method for the evaluation of the cell amount of yeast cultured anaerobically is unaffected by the cultural conditions. 相似文献
75.
76.
Tsuyoshi Sugio Shinji Tanijiri Kyoko Fukuda Kenji Yamaryo Kenji Inagaki Tatsuo Tano 《Bioscience, biotechnology, and biochemistry》2013,77(8):2229-2236
An obligate chemolithoautotroph, Thiobacillus ferrooxidans API 9–3, could utilize amino acids, other than glycine, methionine and phenylalanine, as a sole source of nitrogen. However, both the growth rate and growth yield were lower than those in Fe2+-NH4 -salts medium, suggesting that the ammonium ion was a superior nitrogen source for the strain compared to amino acids. Methionine and phenylalanine strongly inhibited the cell growth on Fe2+-NH4-salts medium at 10 mm. [14C]Glycine could not be taken up into the cells, and this meant the strain could not use glycine as a sole source of nitrogen. The uptake of [14C]leucine into the cells was dependent on the presence of Fe2 +. When the strain was cultured on Fe2 + - leucine (lOmm)-salts medium lacking an inorganic nitrogen source for 5 days at 30°C, 83.5% and 16.5% of the cellular carbon were derived from carbon dioxide and leucine, respectively, indicating that carbon dioxide was a superior carbon source for the bacterium compared to leucine. The ammonium ion did not inhibit the utilization of leucine for cellular carbon. Leucine uptake was markedly inhibited by inhibitors of protein synthesis, such as chloramphenicol (94.3% at 1 mm), streptomycin (57.2% at 5mm) and rifampin (77.2% at 0.1 mm), respectively. Carbon dioxide uptake was also completely inhibited by chloramphenicol at 4mm. These results suggest that the transport of both amino acids and carbon dioxide into the cells was dependent on protein synthesis. 相似文献
77.
Tsuyoshi Fujiwara Shinzo Izumi Patrick J. Brennan 《Bioscience, biotechnology, and biochemistry》2013,77(8):2301-2308
The disaccharide, 2,3-di-O-methyl-4-O-(3,6-di-O-methyl-β-d-glucopyranosyl)-l-rhamno-pyranose, the distal segment of phenolic glycolipid I, that is a specific antigen from Mycobacterium leprae, and some related disaccharides were synthesised as the glycosides of methyl 3-(p-hydroxyphenyl)propionate. The methyl 3-(p-hydroxyphenyl)propionate was coupled with 2,3,4-tri-O-acetyl-l-rhamnosyl bromide, deacetylated, acetonated, coupled with 2,4,6-tri-O-acetyl-3-O-methyl-d-glucosyl bromide, and converted into a variety of p-(2-methoxycarbonylethyl)phenyl 4-O-(3,6-di-O-methyl-d-glucopyranosyl)-containing disaccharides that are amenable to ready conjugation with protein carriers, thereby providing neo-glycoconjugates for the specific serodiagnosis of leprosy. 相似文献
78.
Kazutami Imai Tsuyoshi Sugio Takanori Tsuchida Tatsuo Tano 《Bioscience, biotechnology, and biochemistry》2013,77(7):1349-1354
Effect of heavy metal ions on the growth and the iron-oxidizing activity of Thiobacillus ferrooxidans were investigated.Cupric, zinc, cadmium, and chromium ions had no effect on the growth and the iron-oxidizing activity of cell suspensions or cell-free extracts of the bacterium in high concentrations (10?3~10?2M). Lead ion delayed the start of the growth slightly in 10?3 M, but it did not inhibit the iron-oxidizing activity of the cells in the concentration. Tin and molybdenum oxide ions inhibited both of them in the concentration above 10?3 M.Mercuric mercurous, and silver ions had the most harmful effect. In the concentration of 10?3 .M, each of the cations inhibited almost completely both the growth and the iron-oxidizing activity of the cells.In the experiments with cell-free extracts it was observed that the activity of cytochrome oxidase (cytochrome a597) operating in the iron-oxidizing system of the bacterium was specifically inhibited with mercuric ion in the concentration above 5 × 10?4 M. 相似文献
79.
Tsuyoshi Fujitani 《Bioscience, biotechnology, and biochemistry》2013,77(9):925-930
The critical concentrations of minerals in a growing medium for maximum fermentation of yeast were as follows: P, 1 mmol/1; Mg, 0.2 mmol/1; and K, 1~2 mmol/1. These values are lower than those for the saturation of the cells with each mineral. The order of the concentration for maximum fermentation (K>P>Mg) is in agreement with that for yeast growth.Only a small amount of mineral salt was required to increase the fermentative activity. Very small increase of fermentative activity was observed when the starved yeast was enriched with corresponding minerals by incubating cells with the mineral salt and glucose. 相似文献
80.
Goro Tamura Tamioki Hosoi Jun Aketagawa 《Bioscience, biotechnology, and biochemistry》2013,77(11):2165-2167
The intermediate of the aromatization of 4-oxocyclohexanecar-boxylic acid (OHA) to 4-hydroxybenzoic acid (HA) by Coryne-bacterium cyclohexanicum was identified as (+)-4-oxocyclohex-2-enecarboxylic acid (O2A) using a combined system of gas-liquid chromatography (GLC) and a mass spectrometer and polarimeter. 相似文献