全文获取类型
收费全文 | 1304篇 |
免费 | 81篇 |
出版年
2022年 | 8篇 |
2021年 | 14篇 |
2019年 | 6篇 |
2018年 | 19篇 |
2017年 | 8篇 |
2016年 | 15篇 |
2015年 | 22篇 |
2014年 | 26篇 |
2013年 | 78篇 |
2012年 | 54篇 |
2011年 | 47篇 |
2010年 | 34篇 |
2009年 | 39篇 |
2008年 | 56篇 |
2007年 | 67篇 |
2006年 | 52篇 |
2005年 | 65篇 |
2004年 | 68篇 |
2003年 | 65篇 |
2002年 | 63篇 |
2001年 | 64篇 |
2000年 | 50篇 |
1999年 | 48篇 |
1998年 | 24篇 |
1997年 | 10篇 |
1996年 | 20篇 |
1995年 | 15篇 |
1994年 | 16篇 |
1993年 | 10篇 |
1992年 | 29篇 |
1991年 | 37篇 |
1990年 | 32篇 |
1989年 | 27篇 |
1988年 | 27篇 |
1987年 | 16篇 |
1986年 | 10篇 |
1985年 | 18篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 5篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 10篇 |
1978年 | 10篇 |
1976年 | 13篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 5篇 |
1969年 | 5篇 |
1967年 | 6篇 |
排序方式: 共有1385条查询结果,搜索用时 35 毫秒
61.
Kimura A Ohmichi M Tasaka K Kanda Y Ikegami H Hayakawa J Hisamoto K Morishige K Hinuma S Kurachi H Murata Y 《The Journal of biological chemistry》2000,275(5):3667-3674
Regulation of the mitogen-activated protein kinase (MAPK) family by prolactin-releasing peptide (PrRP) in both GH3 rat pituitary tumor cells and primary cultures of rat anterior pituitary cells was investigated. PrRP rapidly and transiently activated extracellular signal-regulated protein kinase (ERK) in both types of cells. Both pertussis toxin, which inactivates G(i)/G(o) proteins, and exogenous expression of a peptide derived from the carboxyl terminus of the beta-adrenergic receptor kinase I, which specifically blocks signaling mediated by the betagamma subunits of G proteins, completely blocked the PrRP-induced ERK activation, suggesting the involvement of G(i)/G(o) proteins in the PrRP-induced ERK activation. Down-regulation of cellular protein kinase C did not significantly inhibit the PrRP-induced ERK activation, suggesting that a protein kinase C-independent pathway is mainly involved. PrRP-induced ERK activation was not dependent on either extracellular Ca(2+) or intracellular Ca(2+). However, the ERK cascade was not the only route by which PrRP communicated with the nucleus. JNK was also shown to be significantly activated in response to PrRP. JNK activation in response to PrRP was slower than ERK activation. Moreover, to determine whether a MAPK family cascade regulates rat prolactin (rPRL) promoter activity, we transfected the intact rPRL promoter ligated to the firefly luciferase reporter gene into GH3 cells. PrRP activated the rPRL promoter activity in a time-dependent manner. Co-transfection with a catalytically inactive form of a MAPK construct or a dominant negative JNK, partially but significantly inhibited the induction of the rPRL promoter by PrRP. Furthermore, co-transfection with a dominant negative Ets completely abolished the response of the rPRL promoter to PrRP. These results suggest that PrRP differentially activates ERK and JNK, and both cascades are necessary to elicit rPRL promoter activity in an Ets-dependent mechanism. 相似文献
62.
63.
Effect of Active Oxygen Radicals on Protein and Carbohydrate Moieties of Recombinant Human Erythropoietin 总被引:4,自引:0,他引:4
Eriko Uchida Kazushige Morimoto Nana Kawasaki Yokoizaki Ahmed Abdu Said Takao Hayakawa 《Free radical research》1997,27(3):311-323
Our previous study showed that active oxygen radicals generated from a Fenton system and a xanthine plus xanthine oxidase system caused serious loss of in vivo bioactivity of recombinant human erythropoietin (EPO), a highly glycosylated protein. In the present study, we characterized the oxidative modifications to the protein and carbohydrate moiety of EPO, which lead to a reduction of its bioactivity. In vitro bioactivity was reduced when EPO was treated with oxygen radi cals generated from a Fenton system in the presence of 0.016 mM H202, and the reduction was directly proportional to the loss of in vivo bioactivity. SDS-PAGE analysis showed that dimer formation and degradation was observed under more severe conditions (Fenton reaction with 0.16 mM H202). The tryptophan destruction was detected at 0.016 mM H2O2 and well correlated with the loss of in vitro bioactivity, whereas loss of other amino acids were occurred under more severe conditions. Treatment with the Fenton system did not result in any specific damage on the carbohydrate moiety of EPO, except a reduction of sialic acid content under severe condition. These results suggest that active oxygen radicals mainly react with the protein moiety rather than the carbohydrate moiety of EPO. Destruction of tryptophan residues is the most sensitive marker of oxidative damage to EPO, suggesting the importance of tryptophan in the active EPO structure. Deglycosylation of EPO caused an increase of susceptibility to oxygen radicals compared to intact EPO. The role of oligosaccharides in EPO may be to protect the protein structure from active oxygen radicals. 相似文献
64.
T Miyoshi G Ooki M Murata H Hayakawa K Tomita M Imai M Suzuki 《Biochemical and biophysical research communications》1999,265(1):13-17
We have cloned a cDNA inducing a cation-permeable current (mNSC1) from pancreatic beta-cells, which shows niflumate-sensitive current in Xenopus oocytes. To elucidate the expression in mammalian cells, mNSC1 was expressed in CHO cells. The reversal potential by mNSC1 was shifted toward positive which was significantly reversed by flufenamic acid. Single-channel analysis showed a characteristic of a Ca-activated nonselective cation channel. Therefore, we may conclude that mNSC1 expresses a fenamates-sensitive cation channel, inducing membrane depolarization in a mammalian cell. 相似文献
65.
A gene‐driven recovery mechanism: Drosophila larvae increase feeding activity for post‐stress weight recovery
下载免费PDF全文
![点击此处可从《Archives of insect biochemistry and physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Masasuke Ryuda Miku Tabuchi Hitoshi Matsumoto Takashi Matsumura Masanori Ochiai Yoichi Hayakawa 《Archives of insect biochemistry and physiology》2018,97(3)
Recovery from weight loss after stress is important for all organisms, although the recovery mechanisms are not fully understood. We are working to clarify these mechanisms. Here, we recorded enhanced feeding activity of Drosophila melanogaster larvae from 2 to 4 h after heat stress at 35°C for 1 h. During the post‐stress period, expression levels of sweet taste gustatory receptor genes (Grs), Gr5a, Gr43a, Gr64a, and Gr64f, were elevated, whereas bitter taste Grs, Gr66a, and Gr33a, were decreased in expression and expression of a non‐typical taste receptor Gr, Gr68a, was unchanged. Similar upregulation of Gr5a and downregulation of Gr66a was recorded after cold stress at 4°C. Expression levels of tropomyosin and ATP synthase ß subunit were significantly increased in larval mouth parts around 3 to 5 h after the heat stress. We infer that up‐regulation of post‐stress larval feeding activity, and weight recovery, is mediated by increasing capacity for mouth part muscular movements and changes in taste sensing physiology. We propose that Drosophila larvae, and likely insects generally, express an efficient mechanism to recover from weight loss during post‐stress periods. 相似文献
66.
Tsuchiya Kenji Tomioka Noriko Sano Tomoharu Kohzu Ayato Komatsu Kazuhiro Imai Akio Hayakawa Kazuhide Nagata Takamaru Okamoto Takahiro Hirose Yoshinori 《Limnology》2020,21(1):87-96
Limnology - In Lake Biwa, the largest lake in Japan, external pollutant loads have decreased since the 1980s, leading to improved water quality, such as reduction in biochemical oxygen demand (BOD)... 相似文献
67.
Kinoshita Kodzue Indo Yoriko Tajima Tomoyuki Kuze Noko Miyakawa Etsuko Kobayashi Toshio Nakamura Tomoyuki Ogata Mitsuaki Okumura Fumihiko Hayakawa Takashi Morimura Naruki Mori Yusuke Okamoto Munehiro Ozaki Yasuhiko Hirata Satoshi 《Primates; journal of primatology》2021,62(3):475-475
Primates - In the original publication of the article, the coauthor “Takashi Hayakawa” was wrongly assigned as co-corresponding author. 相似文献
68.
Hiroki Kumamoto Hiroyuki Hayakawa Hiromichi Tanaka Satoru Shindoh Keisuke Kato Tadashi Miyasaka 《Nucleosides, nucleotides & nucleic acids》2013,32(1-3):15-27
Abstract Based on the recently developed lithiation-mediated stannyl migration of 6-chloropurine derivatives, 2-iodocordycepin was prepared from cordycepin. The reaction of this compound with terminal alkynes was carried out to synthesize a series of 2-alkynyl derivatives. The vasodilating effect of these compounds was evaluated. 相似文献
69.
Hiroyuki Hayakawa Hiromichi Tanaka Kazuhiro Haraguchi Masami Mayumi Masako Nakajima Takashi Sakamaki 《Nucleosides, nucleotides & nucleic acids》2013,32(1):121-128
Abstract Chlorination of purine nucleosides protected with tert-butyldimethylsilyl (TBDMS) group was examined by the reaction of the C-8 lithiated species, generated by LDA, with p-toluenesulfonyl chloride as an electrophile. This provides a new method for the preparation of 8-chloropurine nucleosides. 相似文献
70.
Parasporin 1Ac2, a Novel Cytotoxic Crystal Protein Isolated from Bacillus thuringiensis B0462 Strain
Shouta Kuroda Anowara Begum Mizue Saga Akina Hirao Eiichi Mizuki Hiroshi Sakai Tohru Hayakawa 《Current microbiology》2013,66(5):475-480
Two novel parasporin (PS) genes were cloned from Bacillus thuringiensis B0462 strain. One was 100 % identical even in nucleotide sequence level with that of parasporin-1Aa (PS1Aa1) from B. thuringiensis A1190 strain. The other (PS1Ac2) showed significant homology (99 % identity) to that of PS1Ac1 from B. thuringiensis 87-29 strain. The 15 kDa (S113–R250) and 60 kDa (I251–S777) fragments consisting of an active form of PS1Ac2 were expressed as His-tag fusion. Upon purification under denaturing condition and refolding, the recombinant polypeptides were applied to cancer cells to analyze their cytotoxicities. 3-(4,5-Dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay revealed that either of 15 or 60 kDa polypeptide exhibited no cytotoxicity to HeLa cells, but they became cytotoxic upon mixed together. Our results suggested that PS1Ac2 was responsible for the cytotoxicity of B. thuringiensis B0462 strain, and that the formation of hetero-dimer of 15 and 60 kDa polypeptide was required for their cytotoxicity. 相似文献