全文获取类型
收费全文 | 1868篇 |
免费 | 84篇 |
国内免费 | 4篇 |
专业分类
1956篇 |
出版年
2021年 | 13篇 |
2020年 | 10篇 |
2019年 | 10篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 42篇 |
2015年 | 46篇 |
2014年 | 61篇 |
2013年 | 126篇 |
2012年 | 111篇 |
2011年 | 127篇 |
2010年 | 76篇 |
2009年 | 60篇 |
2008年 | 103篇 |
2007年 | 112篇 |
2006年 | 132篇 |
2005年 | 110篇 |
2004年 | 124篇 |
2003年 | 114篇 |
2002年 | 112篇 |
2001年 | 28篇 |
2000年 | 32篇 |
1999年 | 27篇 |
1998年 | 25篇 |
1997年 | 28篇 |
1996年 | 20篇 |
1995年 | 18篇 |
1994年 | 17篇 |
1993年 | 14篇 |
1992年 | 23篇 |
1991年 | 19篇 |
1990年 | 14篇 |
1989年 | 21篇 |
1988年 | 15篇 |
1987年 | 12篇 |
1986年 | 8篇 |
1985年 | 9篇 |
1984年 | 14篇 |
1983年 | 14篇 |
1982年 | 10篇 |
1981年 | 9篇 |
1980年 | 4篇 |
1979年 | 9篇 |
1978年 | 6篇 |
1974年 | 4篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1967年 | 3篇 |
1966年 | 4篇 |
1965年 | 5篇 |
排序方式: 共有1956条查询结果,搜索用时 15 毫秒
71.
Kazuyuki Nagamatsu 《Journal of biomolecular structure & dynamics》2013,31(4):729-739
Abstract Fluorophore of proflavine was introduced onto the 3′-terminal ribose moiety of yeast tRNAPhe. The distance between the fluorophore and the fluorescent Y base in the anticodon of yeast tRNAPhe was measured by a singlet-singlet energy transfer. Conformational changes of tRNAPhe with binding of tRNAGlu 2, which has the anticodon UUC complementary to the anticodon GAA of tRNAPhe, were investigated. The distance obtained at the ionic strength of 100 mM K+ and 10 mM Mg2+ is very close to the distance from x-ray diffraction, while the distance obtained in the presence of tRNAGlu 2 is significantly smaller. Further, using a fluorescent probe of 4-bromomethl-7-methoxycoumarin introduced onto pseudouridine residue Ψ55 in the TΨC loop of tRNAPhe, Stern-Volmer quenching experiments for the probe with or without added tRNAGlu 2were carried out. The results showed greater access of the probe to the quencher with added tRNAGlu 2. These results suggest that both arms of the L-shaped tRNA structure tend to bend inside with binding of tRNAGlu 2 and some structural collapse occurs at the corner of the L-shaped structure. 相似文献
72.
Gunnar Dick Chin Lik Tan Joao Nuno Alves Erich M. E. Ehlert Gregory M. Miller Linda C. Hsieh-Wilson Kazuyuki Sugahara Arie Oosterhof Toin H. van Kuppevelt Joost Verhaagen James W. Fawcett Jessica C. F. Kwok 《The Journal of biological chemistry》2013,288(38):27384-27395
Chondroitin sulfate (CS) and the CS-rich extracellular matrix structures called perineuronal nets (PNNs) restrict plasticity and regeneration in the CNS. Plasticity is enhanced by chondroitinase ABC treatment that removes CS from its core protein in the chondroitin sulfate proteoglycans or by preventing the formation of PNNs, suggesting that chondroitin sulfate proteoglycans in the PNNs control plasticity. Recently, we have shown that semaphorin3A (Sema3A), a repulsive axon guidance molecule, localizes to the PNNs and is removed by chondroitinase ABC treatment (Vo, T., Carulli, D., Ehlert, E. M., Kwok, J. C., Dick, G., Mecollari, V., Moloney, E. B., Neufeld, G., de Winter, F., Fawcett, J. W., and Verhaagen, J. (2013) Mol. Cell. Neurosci. 56C, 186–200). Sema3A is therefore a candidate for a PNN effector in controlling plasticity. Here, we characterize the interaction of Sema3A with CS of the PNNs. Recombinant Sema3A interacts with CS type E (CS-E), and this interaction is involved in the binding of Sema3A to rat brain-derived PNN glycosaminoglycans, as demonstrated by the use of CS-E blocking antibody GD3G7. In addition, we investigate the release of endogenous Sema3A from rat brain by biochemical and enzymatic extractions. Our results confirm the interaction of Sema3A with CS-E containing glycosaminoglycans in the dense extracellular matrix of rat brain. We also demonstrate that the combination of Sema3A and PNN GAGs is a potent inhibitor of axon growth, and this inhibition is reduced by the CS-E blocking antibody. In conclusion, Sema3A binding to CS-E in the PNNs may be a mechanism whereby PNNs restrict growth and plasticity and may represent a possible point of intervention to facilitate neuronal plasticity. 相似文献
73.
Takahito Tamai Osamu Yamaguchi Shungo Hikoso Toshihiro Takeda Manabu Taneike Takafumi Oka Jota Oyabu Tomokazu Murakawa Hiroyuki Nakayama Yoshihiro Uno Kyoji Horie Kazuhiko Nishida Nahum Sonenberg Ajay M. Shah Junji Takeda Issei Komuro Kinya Otsu 《The Journal of biological chemistry》2013,288(14):10176-10187
Cardiomyocytes proliferate during fetal life but lose their ability to proliferate soon after birth and further increases in cardiac mass are achieved through an increase in cell size or hypertrophy. Mammalian target of rapamycin complex 1 (mTORC1) is critical for cell growth and proliferation. Rheb (Ras homologue enriched in brain) is one of the most important upstream regulators of mTORC1. Here, we attempted to clarify the role of Rheb in the heart using cardiac-specific Rheb-deficient mice (Rheb−/−). Rheb−/− mice died from postnatal day 8 to 10. The heart-to-body weight ratio, an index of cardiomyocyte hypertrophy, in Rheb−/− was lower than that in the control (Rheb+/+) at postnatal day 8. The cell surface area of cardiomyocytes isolated from the mouse hearts increased from postnatal days 5 to 8 in Rheb+/+ mice but not in Rheb−/− mice. Ultrastructural analysis indicated that sarcomere maturation was impaired in Rheb−/− hearts during the neonatal period. Rheb−/− hearts exhibited no difference in the phosphorylation level of S6 or 4E-BP1, downstream of mTORC1 at postnatal day 3 but showed attenuation at postnatal day 5 or 8 compared with the control. Polysome analysis revealed that the mRNA translation activity decreased in Rheb−/− hearts at postnatal day 8. Furthermore, ablation of eukaryotic initiation factor 4E-binding protein 1 in Rheb−/− mice improved mRNA translation, cardiac hypertrophic growth, sarcomere maturation, and survival. Thus, Rheb-dependent mTORC1 activation becomes essential for cardiomyocyte hypertrophic growth after early postnatal period. 相似文献
74.
75.
Kazuyuki Nakamura Hirofumi Kodera Tenpei Akita Masaaki Shiina Mitsuhiro Kato Hideki Hoshino Hiroshi Terashima Hitoshi Osaka Shinichi Nakamura Jun Tohyama Tatsuro Kumada Tomonori Furukawa Satomi Iwata Takashi Shiihara Masaya Kubota Satoko Miyatake Eriko Koshimizu Kiyomi Nishiyama Mitsuko Nakashima Yoshinori Tsurusaki Noriko Miyake Kiyoshi Hayasaka Kazuhiro Ogata Atsuo Fukuda Naomichi Matsumoto Hirotomo Saitsu 《American journal of human genetics》2013
76.
Keisuke Maruyama Masaharu Nakamura Shusuke Tomoshige Kazuyuki Sugita Makoto Makishima Yuichi Hashimoto Minoru Ishikawa 《Bioorganic & medicinal chemistry letters》2013,23(14):4031-4036
Our multi-template approach for drug discovery, focusing on protein targets with similar fold structures, has yielded lead compounds for various targets. We have also shown that a diphenylmethane skeleton can serve as a surrogate for a steroid skeleton. Here, on the basis of those ideas, we hypothesized that the diphenylmethane derivative bisphenol A (BPA) would bind to the ligand-binding domain of estrogen receptors (ERs) in a similar manner to estradiol and act as a steroid surrogate. To test this idea, we synthesized a series of BPA analogs and evaluated their structure-activity relationships, focusing on agonistic/antagonistic activities at ERs and ERα/ERβ subtype selectivity. Among the compounds examined, 18 was found to be a potent ERα-antagonist with high selectivity over ERβ and androgen receptor under our assay conditions. A computational docking study suggested that 18 would bind to the antagonistic conformation of ERα. ERα-selective antagonists, such as 18, are candidate agents for treatment of breast cancer. 相似文献
77.
Nao Kusuhashi Yukiyasu Tsutsumi Haruo Saegusa Kenji Horie Tadahiro Ikeda Kazumi Yokoyama Kazuyuki Shiraishi 《Proceedings. Biological sciences / The Royal Society》2013,280(1759)
We here describe a new Early Cretaceous (early Albian) eutherian mammal, Sasayamamylos kawaii gen. et sp. nov., from the ‘Lower Formation’ of the Sasayama Group, Hyogo Prefecture, Japan. Sasayamamylos kawaii is characterized by a robust dentary, a distinct angle on the ventral margin of the dentary at the posterior end of the mandibular symphysis, a lower dental formula of 3–4 : 1 : 4 : 3, a robust lower canine, a non-molariform lower ultimate premolar, and a secondarily reduced entoconid on the molars. To date, S. kawaii is the earliest known eutherian mammal possessing only four premolars, which demonstrates that the reduction in the premolar count in eutherians started in the late Early Cretaceous. The occurrence of S. kawaii implies that the relatively rapid diversification of eutherians in the mid-Cretaceous had already started by the early Albian. 相似文献
78.
Kazuyuki Maekawa Yasutaka Miyoshi Kenshiro Tsuru 《Bioscience, biotechnology, and biochemistry》2013,77(10):1951-1956
Dextran was subjected to oxidative scission by periodate, followed by ring closure with nitromethane to form nitrodextran. The nitro group attached to the ring was reduced by LiAlH4 to yield amino-polysaccharide of which the molecular weight was about 10,000. It became clear that nitrodextran consisted of 3-deoxy-3-nitro-mannopyranoside, -glucopyranoside, -galactopyranoside and -talopyranoside and their molar ratio was 6: 5: 1: 2 as determined by column Chromatographic separation and gas Chromatographic analysis of the methanolyzate of nitro-dextran. 相似文献
79.
80.
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)