全文获取类型
收费全文 | 1743篇 |
免费 | 107篇 |
国内免费 | 1篇 |
出版年
2022年 | 7篇 |
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 13篇 |
2018年 | 16篇 |
2017年 | 18篇 |
2016年 | 27篇 |
2015年 | 48篇 |
2014年 | 48篇 |
2013年 | 82篇 |
2012年 | 98篇 |
2011年 | 96篇 |
2010年 | 60篇 |
2009年 | 69篇 |
2008年 | 79篇 |
2007年 | 106篇 |
2006年 | 80篇 |
2005年 | 81篇 |
2004年 | 74篇 |
2003年 | 68篇 |
2002年 | 70篇 |
2001年 | 65篇 |
2000年 | 61篇 |
1999年 | 55篇 |
1998年 | 28篇 |
1997年 | 16篇 |
1996年 | 15篇 |
1995年 | 10篇 |
1994年 | 19篇 |
1993年 | 17篇 |
1992年 | 53篇 |
1991年 | 36篇 |
1990年 | 38篇 |
1989年 | 40篇 |
1988年 | 34篇 |
1987年 | 33篇 |
1986年 | 23篇 |
1985年 | 19篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 9篇 |
1981年 | 12篇 |
1980年 | 8篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 13篇 |
1976年 | 4篇 |
1974年 | 6篇 |
1971年 | 4篇 |
1961年 | 3篇 |
排序方式: 共有1851条查询结果,搜索用时 78 毫秒
231.
Yoshimi Sugiura Kazutaka Araki Shun-ichiro Iemura Tohru Natsume Jun Hoseki Kazuhiro Nagata 《The Journal of biological chemistry》2010,285(10):7135-7142
In the endoplasmic reticulum (ER), a number of thioredoxin (Trx) superfamily proteins are present to enable correct disulfide bond formation of secretory and membrane proteins via Trx-like domains. Here, we identified a novel transmembrane Trx-like protein 4 (TMX4), in the ER of mammalian cells. TMX4, a type I transmembrane protein, was localized to the ER and possessed a Trx-like domain that faced the ER lumen. A maleimide alkylation assay showed that a catalytic CXXC motif in the TMX4 Trx-like domain underwent changes in its redox state depending on cellular redox conditions, and, in the normal state, most of the endogenous TMX4 existed in the oxidized form. Using a purified recombinant protein containing the Trx-like domain of TMX4 (TMX4-Trx), we confirmed that this domain had reductase activity in vitro. The redox potential of this domain (−171.5 mV; 30 °C at pH 7.0) indicated that TMX4 could work as a reductase in the environment of the ER. TMX4 had no effect on the acceleration of ER-associated degradation. Because TMX4 interacted with calnexin and ERp57 by co-immunoprecipitation assay, the role of TMX4 may be to enable protein folding in cooperation with these proteins consisting of folding complex in the ER. 相似文献
232.
Takeshi Kawakubo Shuichi Karita Yuko Araki Shota Watanabe Masafumi Oyadomari Rie Takada Fumio Tanaka Kentaro Abe Takahito Watanabe Yoichi Honda Takashi Watanabe 《Biotechnology and bioengineering》2010,105(3):499-508
In enzymatic saccharification of lignocellulosics, the access of the enzymes to exposed cellulose surfaces is a key initial step in triggering hydrolysis. However, knowledge of the structure–hydrolyzability relationship of the pretreated biomass is still limited. Here we used fluorescent‐labeled recombinant carbohydrate‐binding modules (CBMs) from Clostridium josui as specific markers for crystalline cellulose (CjCBM3) and non‐crystalline cellulose (CjCBM28) to analyze the complex surfaces of wood tissues pretreated with NaOH, NaOH–Na2S (kraft pulping), hydrothermolysis, ball‐milling, and organosolvolysis. Japanese cedar wood, one of the most recalcitrant softwood species was selected for the analysis. The binding analysis clarified the linear dependency of the exposure of crystalline and non‐crystalline cellulose surfaces for enzymatic saccharification yield by the organosolv and kraft delignification processes. Ball‐milling for 5–30 min increased saccharification yield up to 77%, but adsorption by the CjCBM–cyan fluorescent proteins (CFPs) was below 5%. Adsorption of CjCBM–CFPs on the hydrothermolysis pulp were less than half of those for organosolvolysis pulp, in coincidence with low saccharification yields. For all the pretreated wood, crystallinity index was not directly correlated with the overall saccharification yield. Fluorescent microscopy revealed that CjCBM3–CFP and CjCBM28–CFP were site‐specifically adsorbed on external fibrous structures and ruptured or distorted fiber surfaces. The assay system with CBM–CFPs is a powerful measure to estimate the initiation sites of hydrolysis and saccharification yields from chemically delignified wood pulps. Biotechnol. Bioeng. 2010; 105: 499–508. © 2009 Wiley Periodicals, Inc. 相似文献
233.
Takuma Kobayashi Kunio Yasuda Masasuke Araki 《Development, growth & differentiation》2010,52(4):351-363
Dorsal and ventral specification in the early optic vesicle plays a crucial role in vertebrate ocular morphogenesis, and proper dorsal‐ventral polarity in the optic vesicle ensures that distinct structures develop in separate domains within the eye primordium. The polarity is determined progressively during development by coordinated regulation of extraocular dorsal and ventral factors. In the present study, we cultured discrete portions of embryonic chick brains by preparing anterior cephalon, anterior dorsal cephalon and anterior ventral cephalon, and clearly demonstrate that bone morphogenetic protein 4 (BMP4) and Sonic hedgehog (Shh) constitute a dorsal‐ventral signaling system together with fibroblast growth factor 8 (FGF8). BMP4 and Shh upregulate Tbx5 and Pax2, as reported previously, and at the same time Shh downregulates Tbx5, while BMP4 affects Pax2 expression to downregulate similarly. Shh induces Fgf8 expression in the ventral optic vesicle. This, in turn, determines the distinct boundary of the retinal pigmented epithelium and the neural retina by suppressing Mitf expression. The lens develops only when signals from both the dorsal and ventral regions come across together. Inverted deposition of Shh and BMP4 signals in organ‐cultured optic vesicle completely re‐organized ocular structures to be inverted. Based on these observations we propose a novel model in which the two signals govern the whole of ocular development when they encounter each other in the ocular morphogenic domain. 相似文献
234.
Bey EA Wuerzberger-Davis SM Pink JJ Yang CR Araki S Reinicke KE Bentle MS Dong Y Cataldo E Criswell TL Wagner MW Li L Gao J Boothman DA 《Journal of cellular physiology》2006,209(3):604-610
Work from the laboratory of Dr. Arthur B. Pardee has highlighted basic principles that govern cellular and molecular biological processes in living cells. Among the most important governing principles in cellular and molecular responses are: (i) threshold "restriction" responses, wherein a level of response is reached and a "point of no return" is achieved; (ii) feedback regulation; and (iii) redundancy. Lessons learned from the molecular biology of cellular stress responses in mammalian cancer versus normal cells after ionizing radiation (IR) or chemotherapeutic agent exposures reveal similar instances of these guiding principles in mammalian cells. Among these are the: (i) induction of cell death responses by beta-lapachone (beta-lap), a naphthoquinone anti-tumor agent that kills cancer cells via an NQO1 (i.e., X-ray-inducible protein-3, xip3)-dependent mechanism; (ii) induction of secretory clusterin (sCLU) in response to TGF-beta1 exposure, and the ability of induced sCLU protein to down-regulate TGF-beta1 signaling; and (iii) induction of DNA mismatch repair-dependent G(2) cell cycle checkpoint responses after exposure to alkylating agents. We have learned these lessons and now adopted strategies to exploit them for improved therapy. These examples will be discussed and compared to the pioneering findings of researchers in the Pardee laboratory over the years. 相似文献
235.
Nakayama Y Nakajima Y Kato N Takai H Kim DS Arai M Mezawa M Araki S Sodek J Ogata Y 《Journal of cellular physiology》2006,208(2):326-335
236.
237.
Hiroshi Takashima Ayako Araki Keiko Takemoto Naokazu Yoshikawa Keiichi Tsukahara 《Journal of biological inorganic chemistry》2006,11(3):316-324
In order to understand the detailed mechanism of the stereoselective photoinduced electron-transfer (ET) reactions of zinc-substituted
myoglobin (ZnMb) with optically active molecules by flash photolysis, we designed and prepared new optically active agents,
such as N,N′-dimethylcinchoninium diiodide ([MCN]I2) and N,N′-dimethylcinchonidinium diiodide ([MCD]I2). The photoexcited triplet state of ZnMb, 3(ZnMb)*, was successfully quenched by [MCN]2+ and [MCD]2+ ions to form the radical pair of ZnMb cation (ZnMb·+) and reduced [MCN]·+ and [MCD]·+, followed by a thermal back ET reaction to the ground state. The rate constants (k
q) for the ET quenching at 25 °C were obtained as k
q(MCN)=(1.9±0.1)×106 M−1 s−1 and k
q(MCD)=(3.0±0.2)×106 M−1 s−1, respectively. The ratio of k
q(MCD)/k
q(MCN)=1.6 indicates that the [MCD]2+ preferentially quenches 3(ZnMb)*. The second-order rate constants (k
b) for the thermal back ET reaction from [MCN]·+ and [MCD]·+ to ZnMb·+ at 25 °C were k
b(MCN)=(0.79±0.04)×108 M−1 s−1 and k
b(MCD)=(1.0±0.1)×108 M−1 s−1, respectively, and the selectivity was k
q(MCD)/k
q(MCN)=1.3. Both quenching and thermal back ET reactions are controlled by the ET step. In the quenching reaction, the energy
differences of ΔΔH
≠(MCD–MCN) and ΔΔS
≠(MCD–MCN) at 25 °C were obtained as −1.1 and 0 kJ mol−1, respectively. On the other hand, ΔΔH
≠(MCD–MCN)=11±2 kJ mol−1 and TΔΔS
≠(MCD–MCN)=−10±2 kJ mol−1 were given in the thermal back ET reaction. The highest stereoselectivity of 1.7 for [MCD]·+ found at low temperature (10 °C) was due to the ΔΔS
≠ value obtained in the thermal back ET reaction.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
238.
239.
Mizuho Kusuda Mitsuhiro Ueda Yasuhito Konishi Yoshihito Araki Katsuji Yamanaka Masami Nakazawa Kazutaka Miyatake Takao Terashita 《Mycoscience》2006,47(4):184-189
We investigated extracellular carbohydrase production in the medium of an ectomycorrhizal fungus, Tricholoma matsutake, to reveal its ability to utilize carbohydrates such as starch as a growth substrate and to survey the saprotrophic aspects.
We found β-glucosidase activity in the static culture filtrate of this fungus. The β-glucosidase was purified and characterized.
The purified enzyme was obtained from about 2.1 l static culture filtrate, with 9.0% recovery, and showed a single protein
band on SDS-PAGE. Molecular mass was about 160 kDa. The enzyme was most active around 60°C and pH 5.0, and stable over a pH
of 4.0–8.0 for 30 min at 37°C. The purified enzyme was activated by the presence of Ca2+ and Mn2+ ions (about 2–3 times that of the control). The enzyme readily hydrolyzed oligosaccharides having a β-1,4-glucosidic linkage
such as cellobiose and cellotriose. However, it did not hydrolyze polysaccharides such as avicel and CM-cellulose or oligosaccharides
having an α-glucosidic linkage. Moreover, cellotriose was hydrolyzed by the enzyme for various durations, and the resultant
products were analyzed by TLC. We concluded that the enzyme from T. matsutake seems to be a β-glucosidase because cellotriose with a β-1,4-glucosidic linkage decomposed to glucose during the enzyme reaction. 相似文献
240.
Wilson TJ Ouellet J Zhao ZY Harusawa S Araki L Kurihara T Lilley DM 《RNA (New York, N.Y.)》2006,12(6):980-987
RNA catalysis is important in the processing and translation of RNA molecules, yet the mechanisms of catalysis are still unclear in most cases. We have studied the role of nucleobase catalysis in the hairpin ribozyme, where the scissile phosphate is juxtaposed between guanine and adenine bases. We show that a modified ribozyme in which guanine 8 has been substituted by an imidazole base is active in both cleavage and ligation, with ligation rates 10-fold faster than cleavage. The rates of both reactions exhibit bell-shaped dependence on pH, with pK(a) values of 5.7 +/- 0.1 and 7.7 +/- 0.1 for cleavage and 6.1 +/- 0.3 and 6.9 +/- 0.3 for ligation. The data provide good evidence for general acid-base catalysis by the nucleobases. 相似文献