全文获取类型
收费全文 | 1588篇 |
免费 | 141篇 |
出版年
2020年 | 11篇 |
2019年 | 10篇 |
2018年 | 17篇 |
2017年 | 21篇 |
2016年 | 22篇 |
2015年 | 28篇 |
2014年 | 50篇 |
2013年 | 79篇 |
2012年 | 64篇 |
2011年 | 75篇 |
2010年 | 42篇 |
2009年 | 42篇 |
2008年 | 82篇 |
2007年 | 91篇 |
2006年 | 67篇 |
2005年 | 76篇 |
2004年 | 86篇 |
2003年 | 74篇 |
2002年 | 62篇 |
2001年 | 64篇 |
2000年 | 62篇 |
1999年 | 41篇 |
1998年 | 24篇 |
1997年 | 20篇 |
1996年 | 19篇 |
1995年 | 17篇 |
1994年 | 15篇 |
1993年 | 15篇 |
1992年 | 32篇 |
1991年 | 42篇 |
1990年 | 38篇 |
1989年 | 26篇 |
1988年 | 34篇 |
1987年 | 28篇 |
1986年 | 22篇 |
1985年 | 21篇 |
1984年 | 9篇 |
1983年 | 13篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 15篇 |
1979年 | 13篇 |
1977年 | 12篇 |
1975年 | 10篇 |
1974年 | 14篇 |
1973年 | 16篇 |
1971年 | 10篇 |
1970年 | 17篇 |
1969年 | 13篇 |
1967年 | 8篇 |
排序方式: 共有1729条查询结果,搜索用时 31 毫秒
1.
Chie Amano Hideki Minematsu Kazuyo Fujita Shinki Iwashita Masaki Adachi Koichi Igarashi Shuji Hinuma 《PloS one》2015,10(9)
To explore a novel method using liposomes to suppress macrophages, we screened food constituents through cell culture assays. Curcumin was one of the strongest compounds exhibiting suppressive effects on macrophages. We subsequently tried various methods to prepare liposomal curcumin, and eventually succeeded in preparing liposomes with sufficient amounts of curcumin to suppress macrophages by incorporating a complex of curcumin and bovine serum albumin. The diameter of the resultant nanoparticles, the liposomes containing curcumin, ranged from 60 to 100 nm. Flow cytometric analyses revealed that after intraperitoneal administration of the liposomes containing curcumin into mice, these were incorporated mainly by macrophages positive for F4/80, CD36, and CD11b antigens. Peritoneal cells prepared from mice injected in vivo with the liposomes containing curcumin apparently decreased interleukin-6-producing activities. Major changes in body weight and survival rates in the mice were not observed after administrating the liposomes containing curcumin. These results indicate that the liposomes containing curcumin are safe and useful for the selective suppression of macrophages in vivo in mice. 相似文献
2.
3.
4.
Kiyohiko Sugano 《化学与生物多样性》2009,6(11):2014-2029
Bile micelles play an important role in oral absorption of low‐solubility compounds. Bile micelles can affect solubility, dissolution rate, and permeability. For the pH–solubility profile in bile micelles, the Henderson–Hasselbalch equation should be modified to take bile‐micelle partition into account. For the dissolution rate, in the Nernst–Brunner equation, the effective diffusion coefficient in bile‐micelle media should be used instead of the monomer diffusion coefficient. The diffusion coefficient of bile micelles is 8‐ to 18‐fold smaller than that of monomer molecules. For permeability, the effective diffusion coefficient in the unstirred water layer adjacent to the epithelial membrane, and the free fraction at the epithelial membrane surface should be taken into account. The importance of these aspects is demonstrated here using several in vivo and clinical oral‐absorption data of low‐solubility model compounds. Using the theoretical equations, the food effect on oral absorption is further discussed. 相似文献
5.
Masafumi Komiya Shigehiro Asano Nobuyuki Koike Erina Koga Junetsu Igarashi Shogo Nakatani Yoshiaki Isobe 《Bioorganic & medicinal chemistry》2012,20(23):6840-6847
Based on 2-(4-phenoxybenzoyl)-5-hydroxyindole (2), a novel structural class of CaMKII inhibitors were synthesized and further optimized. The strong acidity of the hydroxyl group and the lipophilic group at the 4 and 6-positions were found to be necessary for strong CaMKII inhibition. Compound 25 was identified as a promising compound with 50-fold more potent inhibitory activity for CaMKII than 2. Compound 25 also showed high selectivity for CaMKII over off-target kinases. 相似文献
6.
7.
Ken Igarashi Jun’ichi Oda Yuzo Inouye Minoru Ohno 《Bioscience, biotechnology, and biochemistry》2013,77(5):811-812
About 30 dipeptides and some tripeptides were led to new benzimidazole derivatives by incorporating their carboxyl groups into benzimidazole ring by the reaction with o-phenylenediamine. The ring closure to benzimidazole was well achieved by heating mildly at a moderate temperature in acetic acid.Some benzimidazole derivatives of peptides had remarkable phytotoxicities. 相似文献
8.
Enzymatic synthesis of N,N-dimethyl-sphingosine: demonstration of the sphingosine: N-methyltransferase in mouse brain 总被引:3,自引:0,他引:3
Based on our recent finding that N,N-dimethyl-D-erythro-sphingenine strongly inhibits protein kinase C (PK-C) whereas D-erythro-sphingenine produces only weak inhibition, we have studied the presence of N-methyltransferase responsible for conversion of sphingosine to its N,N-dimethyl derivative. The enzyme activity was detected in crude mouse brain tissue homogenate but was hardly detectable in liver homogenate, in which N-methylation of phosphatidylethanolamine (PE) is predominant. 相似文献
9.
Masako Nomaguchi Masaru Yokoyama Ken Kono Emi E. Nakayama Tatsuo Shioda Naoya Doi Sachi Fujiwara Akatsuki Saito Hirofumi Akari Kei Miyakawa Akihide Ryo Hirotaka Ode Yasumasa Iwatani Tomoyuki Miura Tatsuhiko Igarashi Hironori Sato Akio Adachi 《Journal of virology》2013,87(21):11447-11461
Human immunodeficiency virus type 1 (HIV-1) replication in macaque cells is restricted mainly by antiviral cellular APOBEC3, TRIM5α/TRIM5CypA, and tetherin proteins. For basic and clinical HIV-1/AIDS studies, efforts to construct macaque-tropic HIV-1 (HIV-1mt) have been made by us and others. Although rhesus macaques are commonly and successfully used as infection models, no HIV-1 derivatives suitable for in vivo rhesus research are available to date. In this study, to obtain novel HIV-1mt clones that are resistant to major restriction factors, we altered Gag and Vpu of our best HIV-1mt clone described previously. First, by sequence- and structure-guided mutagenesis, three amino acid residues in Gag-capsid (CA) (M94L/R98S/G114Q) were found to be responsible for viral growth enhancement in a macaque cell line. Results of in vitro TRIM5α susceptibility testing of HIV-1mt carrying these substitutions correlated well with the increased viral replication potential in macaque peripheral blood mononuclear cells (PBMCs) with different TRIM5 alleles, suggesting that the three amino acids in HIV-1mt CA are involved in the interaction with TRIM5α. Second, we replaced the transmembrane domain of Vpu of this clone with the corresponding region of simian immunodeficiency virus SIVgsn166 Vpu. The resultant clone, MN4/LSDQgtu, was able to antagonize macaque but not human tetherin, and its Vpu effectively functioned during viral replication in a macaque cell line. Notably, MN4/LSDQgtu grew comparably to SIVmac239 and much better than any of our other HIV-1mt clones in rhesus macaque PBMCs. In sum, MN4/LSDQgtu is the first HIV-1 derivative that exhibits resistance to the major restriction factors in rhesus macaque cells. 相似文献
10.
Toko Tanikawa Yasuhiro Hirano Masako Dannoura Keitarou Yamase Kenji Aono Masahiro Ishii Tetsurou Igarashi Hidetoshi Ikeno Yoichi Kanazawa 《Plant and Soil》2013,373(1-2):317-327