全文获取类型
收费全文 | 3376篇 |
免费 | 241篇 |
出版年
2022年 | 10篇 |
2021年 | 27篇 |
2020年 | 20篇 |
2019年 | 24篇 |
2018年 | 30篇 |
2017年 | 26篇 |
2016年 | 58篇 |
2015年 | 78篇 |
2014年 | 93篇 |
2013年 | 235篇 |
2012年 | 198篇 |
2011年 | 168篇 |
2010年 | 116篇 |
2009年 | 121篇 |
2008年 | 205篇 |
2007年 | 198篇 |
2006年 | 188篇 |
2005年 | 170篇 |
2004年 | 213篇 |
2003年 | 182篇 |
2002年 | 190篇 |
2001年 | 68篇 |
2000年 | 52篇 |
1999年 | 62篇 |
1998年 | 50篇 |
1997年 | 47篇 |
1996年 | 32篇 |
1995年 | 38篇 |
1994年 | 24篇 |
1993年 | 36篇 |
1992年 | 61篇 |
1991年 | 61篇 |
1990年 | 50篇 |
1989年 | 39篇 |
1988年 | 42篇 |
1987年 | 34篇 |
1986年 | 22篇 |
1985年 | 37篇 |
1984年 | 47篇 |
1983年 | 25篇 |
1982年 | 23篇 |
1981年 | 22篇 |
1980年 | 21篇 |
1979年 | 19篇 |
1978年 | 20篇 |
1977年 | 13篇 |
1976年 | 22篇 |
1975年 | 15篇 |
1974年 | 12篇 |
1973年 | 12篇 |
排序方式: 共有3617条查询结果,搜索用时 15 毫秒
141.
Takaaki Kubota Yuichiro Ishiguro Azusa Takahashi-Nakaguchi Jane Fromont Tohru Gonoi Jun’ichi Kobayashi 《Bioorganic & medicinal chemistry letters》2013,23(1):244-247
Three new polyketides, manzamenones L–N (1–3), have been isolated from an Okinawan marine sponge of the genus Plakortis. The structures of 1–3 were elucidated on the basis of spectroscopic data. Manzamenones L–N (1–3) were new dimeric fatty-acid derivatives consisting of a tetrahydroindenone with three carboxy groups and two hexadecanyl chains. Manzamenones M (2) and N (3) showed antimicrobial activity against several bacteria and fungi. 相似文献
142.
143.
Masaki Setoguchi Shin Iimura Yuuichi Sugimoto Yoshiyuki Yoneda Jun Chiba Toshiyuki Watanabe Fumihito Muro Yutaka Iigo Gensuke Takayama Mika Yokoyama Tomoe Taira Misato Aonuma Tohru Takashi Atsushi Nakayama Nobuo Machinaga 《Bioorganic & medicinal chemistry》2013,21(1):42-61
We have carried out the optimization of substituents at the C-3 or the C-5 position on the pyrrolidine ring of VLA-4 antagonist 3 with 2-(phenylamino)-7-fluorobenzoxazolyl moiety for the purpose of improving in vivo efficacy while maintaining good aqueous solubility. As a result, we successfully increased in vitro activity in the presence of 3% human serum albumin and achieved an exquisite lipophilic and hydrophilic balance of compounds suitable for oral administrative regimen. The modification resulted in the identification of zwitterionic compound 7n with (5S)-[methoxy(methyl)amino]methylpyrrolidine, which significantly alleviated bronchial hyper-responsiveness to acetylcholine chloride at 12.5 mg/kg, p.o. in a murine asthma model and showed favorable aqueous solubility (JP1, 89 μg/mL; JP2, 462 μg/mL). Furthermore, this compound showed good oral bioavailability (F = 54%) in monkeys. 相似文献
144.
Refeeding with a standard diet after a 48-h fast elicits an inflammatory response in the mouse liver
Motoko Oarada Takashi Miki Shohei Kohno Kanae Sakai Takeshi Nikawa Mitsutoshi Yoneyama Tohru Gonoi 《The Journal of nutritional biochemistry》2013,24(7):1314-1323
Unhealthy eating behaviors increase the risk of metabolic diseases, but the underlying mechanisms are not fully elucidated. Because inflammation contributes to the pathogenesis of metabolic diseases, it is important to understand the effects of unhealthy eating on the inflammatory state. The objective of our present study was to address the effects of a fasting–refeeding regime, a model of irregular eating, on the hepatic inflammatory responses in mouse. The animals were fasted for 48 h and then refed either a standard or low-carbohydrate/high-fat diet. Inflammatory gene expression in the liver was then sequentially measured for the first 17 h after initiation of refeeding. To assess the roles of dietary carbohydrates and toll-like receptor 2 (TLR2) in the refeeding-induced inflammatory changes, gene expression levels in mice refed only carbohydrates (α-corn starch and sucrose) at different doses and in TLR2-deficient mice refed a standard diet were also analyzed. Refeeding with a standard diet increased the liver expression of Tlr2, proinflammatory mediators (Cxcl10, Cxcl1, Cxcl2, Icam-1) and negative regulators of TLR-signaling (A20 and Atf3). These increases were attenuated in mice refed a low-carbohydrate/high-fat diet. Refeeding only α-corn starch and sucrose also increased the expression of these inflammatory pathway genes depending on the doses. TLR2 deficiency significantly attenuated the refeeding-induced increase in the liver expression of Cxcl10, Cxcl1, Icam-1 and A20. These findings suggest that an irregular eating behavior can elicit a liver inflammatory response, which is at least partly mediated by TLR2, and that dietary carbohydrates play critical roles in this process. 相似文献
145.
Miki Kinoshita Noritaka Hara Katsumi Imada Keiichi Namba Tohru Minamino 《Molecular microbiology》2013,90(6):1249-1261
Assembly of the bacterial flagellar filament is strictly sequential; the junction proteins, FlgK and FlgL, are assembled at the distal end of the hook prior to the FliD cap, which supports assembly of as many as 30 000 FliC molecules into the filament. Export of these proteins requires assistance of flagellar chaperones: FlgN for FlgK and FlgL, FliT for FliD and FliS for FliC. The C‐terminal cytoplasmic domain of FlhA (FlhAC), a membrane component of the export apparatus, provides a binding‐site for these chaperone–substrate complexes but it remains unknown how it co‐ordinates flagellar protein export. Here, we report that the highly conserved hydrophobic dimple of FlhAC is involved in the export of FlgK, FlgL, FliD and FliC but not in proteins responsible for the structure and assembly of the hook, and that the binding affinity of FlhAC for the FlgN/FlgK complex is slightly higher than that for the FliT/FliD complex and about 14‐fold higher than that for the FliS/FliC complex, leading to the proposal that the different binding affinities of FlhAC for these chaperone/substrate complexes may confer an advantage for the efficient formation of the junction and cap structures at the tip of the hook prior to filament formation. 相似文献
146.
Yasuji Minoda Hisashi Yamagata Tohru Kodama 《Bioscience, biotechnology, and biochemistry》2013,77(7):1829-1830
Strains producing higher levels of cellulolytic enzymes were selected from among 520 strains of plant pathogenic fungi, Fusarium species, and F. oxysporum strain SUF850 was found to be the best producer. When strain SUF850 was cultured using one of three polysaccharides, Avicel, carboxy- methyl cellulose (CMC) or xylan, as a carbon source, the culture filtrate contained degrading activi- ties toward all three substrates, i.e., irrespective of the carbon source used. From the culture filtrate of Avicel-grown cells, four distinct enzymes were purified to homogeneity, as judged on SDS-PAGE. They were designated as CMCase I, CMCase II, /Miitrophenyl-β-d-cellobiosidase and xylanase, and the characteristics of the individual enzymes were examined and compared. 相似文献
147.
Toshiko Kido Katsuyuki Tanizawa Kenji Inagaki Tohru Yoshimura Masaaki Ishida Katsumi Hashizume 《Bioscience, biotechnology, and biochemistry》2013,77(10):2549-2554
2-Nitropropane dioxygenase, purified to homogeneity by an improved method from a yeast, Hansenula mrakii, has a molecular weight of 42,000, and consists of a single polypeptide. The enzyme contains 1 mol of FAD per mol of enzyme. The iron protein associated with previous preparations was removed by the present purification procedures. The enzyme catalyzes the oxygenative denitrification of anionic nitroalkanes much more effectively than that of the neutral ones with the optimum pH of 6.5. The Michaelis constants for the anionic substrates are as follows: 2-nitropropane, 1.61 mM; 1-nitropropane, 3.23 mM; nitroethane, 3.13 mM, and 3-nitro-2-butanol, 0.59 mM. 相似文献
148.
Junji Morita Naoki Kashimura Tohru Komano 《Bioscience, biotechnology, and biochemistry》2013,77(4):883-890
The inactivation of bacteriophage ?X174 by d-fructose 6-phosphate was investigated. This inactivation was inhibited by EDTA or reducing agents, and stimulated by Cu2+ but other metal ions could not be substituted for Cu2+. The reaction was also inhibited by superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6) and various free radical scavengers.No detectable changes were observed in adsorption capacity of phage and in the conformation of the virion. The viral DNA in the virion was, however, found to be cleaved. This strand scission was also enhanced by Cu2+ and protected by catalase. Similar results were obtained when ?X174 DNA was directly treated with d-fructose 6-phosphate.It is concluded that the inactivation of ?X174 is due to DNA strand scission in the virion by the free radical of d-fructose 6-phosphate or oxygen radicals generated during autoxidation of d-fructose 6-phosphate. 相似文献
149.
Atsushi Higashi Junji Morita Hiroshi Sakai Tohru Komano 《Bioscience, biotechnology, and biochemistry》2013,77(10):2093-2094
The fluorescent antibody technique was used to trace an inoculated Nocardia erythropolis strain which was capable of rapidly degrading phthalate esters in soil column and activated sludge systems. The reaction of antibody to Nocardia erythropolis S-1 was highly strain specific, i. e., only one of twelve other strain of N. erythropolis was stained with this fluorescent antibody. All other species of Nocardia and other genera of bacteria and a strain of Candida were not stained. Using this technique it was demonstrated that N. erythropolis S-1 inoculated into activated sludge and soil column systems was successfully distinguished from many other microorganisms in mixed culture systems, and the distribution of this strain was appreciated. 相似文献
150.
Michio Himeno Naoto Koyama Tomohiko Funato Tohru Komano 《Bioscience, biotechnology, and biochemistry》2013,77(5):1461-1468
Cultured insect cells, TN-368 from the cabbage looper, swelled and burst upon treatment with the enzyme-digested delta-endotoxin of Bacillus thuringiensis var. aizawai. The cytotoxic sweelling was depended upon the amount of the delta-endotoxin added and the concentration of NaCl or KC1 in the isotonic solution. The concentration of Na+ in the swollen cells approximately doubled in isotonic NaCl, while that of K+ decreased to 10% of the original cellular concentration. The cell swelling was inhibited by tetrodotoxin and also by ouabain in only KC1 isotonic solution. On the other hand, 4-aminopyridine stimulated the swelling in the isotonic KC1 solution, These results indicate that the delta-endotoxin induces the stimulation of Na+ influx and K+ efflux in the isotonic NaCl solution, and also stimulates the Na+, K+-ATPase in the isotonic KC1 solution. The cytotoxic swelling was also blocked by cAMP, AMP, ATP, GTP, and NAD, but not by adenosine and GMP. These results suggest the participation of nucleotide derivatives in the action of delta-endotoxin. 相似文献