全文获取类型
收费全文 | 4958篇 |
免费 | 326篇 |
国内免费 | 3篇 |
出版年
2021年 | 36篇 |
2020年 | 20篇 |
2019年 | 32篇 |
2018年 | 51篇 |
2017年 | 44篇 |
2016年 | 70篇 |
2015年 | 108篇 |
2014年 | 128篇 |
2013年 | 248篇 |
2012年 | 231篇 |
2011年 | 226篇 |
2010年 | 139篇 |
2009年 | 144篇 |
2008年 | 222篇 |
2007年 | 220篇 |
2006年 | 210篇 |
2005年 | 231篇 |
2004年 | 203篇 |
2003年 | 250篇 |
2002年 | 216篇 |
2001年 | 197篇 |
2000年 | 216篇 |
1999年 | 174篇 |
1998年 | 69篇 |
1997年 | 59篇 |
1996年 | 49篇 |
1995年 | 53篇 |
1994年 | 48篇 |
1993年 | 51篇 |
1992年 | 117篇 |
1991年 | 116篇 |
1990年 | 105篇 |
1989年 | 109篇 |
1988年 | 100篇 |
1987年 | 74篇 |
1986年 | 76篇 |
1985年 | 51篇 |
1984年 | 65篇 |
1983年 | 50篇 |
1982年 | 42篇 |
1981年 | 33篇 |
1980年 | 22篇 |
1979年 | 43篇 |
1978年 | 34篇 |
1977年 | 31篇 |
1976年 | 26篇 |
1974年 | 33篇 |
1973年 | 21篇 |
1971年 | 27篇 |
1970年 | 29篇 |
排序方式: 共有5287条查询结果,搜索用时 31 毫秒
971.
Intrasteric regulation of MDM2 总被引:1,自引:0,他引:1
972.
The metabolic regulation of Escherichia coli lacking a functional pykF gene was investigated based on gene expressions, enzyme activities, intracellular metabolite concentrations and the metabolic flux distribution obtained based on (13)C-labeling experiments. RT-PCR revealed that the glycolytic genes such as glk, pgi, pfkA and tpiA were down regulated, that ppc, pckA, maeB and mdh genes were strongly up-regulated, and that the oxidative pentose phosphate pathway genes such as zwf and gnd were significantly up-regulated in the pykF mutant. The catabolite repressor/activator gene fruR was up-regulated in the pykF mutant, but the adenylate cyclase gene cyaA was down-regulated indicating a decreased rate of glucose uptake. This was also ascertained by the degradation of ptsG mRNA, the gene for which was down-regulated in the pykF mutant. In general, the changes in enzyme activities more or less correlated with ratios of gene expression, while the changes in metabolic fluxes did not correlate with enzyme activities. For example, high flux ratios were obtained through the oxidative pentose phosphate pathway due to an increased concentration of glucose-6-phosphate rather than to favorable enzyme activity ratios. In contrast, due to decreased availability of pyruvate (and acetyl coenzyme A) in the pykF mutant compared with the wild type, low flux ratios were found through lactate and acetate forming pathways. 相似文献
973.
Bengea S Araki Y Ito O Igarashi J Sagami I Shimizu T 《Journal of inorganic biochemistry》2004,98(7):1210-1216
The effects of substrates, inhibitors and tetrahydrobiopterin (H4B) on CO rebinding to the isolated heme-bound oxygenase domain (nNOSox) of neuronal nitric oxide synthase were examined by laser flash photolysis. The rate constant of CO recombination with substrate and inhibitor-free nNOSox in the absence of H4B was 1.0 x 10(6) M(-1) s(-1). The addition of H4B led to a marked decrease in the rate to 0.59 x 10(6) M(-1) s(-1). Interestingly, the substrates, L-Arg and N-hydroxy-L-Arg (NHA), altered CO binding behavior in that the binding rate was modified to CO concentration-independent, both with and without H4B. In the absence of H4B, agmatine, NG-monomethyl-L-Arg (NMMA) and NG-nitro-L-Arg methyl ester (NAME) decreased the CO concentration-dependent rate constants of rebinding by half (0.43 x 10(6) M(-1) s(-1) for the NMMA-bound complex), whereas N6-(l-iminoethyl)-L-Lys (NIL) and 7-nitro-1H-indazole (7-NI) increased the rate constants by more than 70% (up to 2.1 x 10(6) M(-1) s(-1) for the NIL-bound complex). In the presence of H4B, the binding rate was independent of CO concentration for the agmatine-bound complex. The differential effects of the inhibitors on the CO concentration-dependent rate constants were significantly diminished for the H4B-bound system. Interestingly, these variable effects of inhibitors on the CO binding rate were more pronounced in the absence of H4B. Accordingly, we suggest that H4B significantly influences CO binding by altering the CO access channel, and further reduces the divergent effects of different inhibitors. 相似文献
974.
Sato T Shimizu T Watarai M Kobayashi M Kano S Hamabata T Takeda Y Yamasaki S 《Gene》2003,309(1):35-48
Shiga toxin 2-converting phage was isolated from Escherichia coli O157:H7 associated with an outbreak that occurred in Okayama, Japan in 1996 (M. Watarai, T. Sato, M. Kobayashi, T. Shimizu, S. Yamasaki, T. Tobe, C. Sasakawa and Y. Takeda, Infect. Immun. 61 (1998) 3210-3204). In this study, we analyzed the complete nucleotide sequence of Shiga toxin 2-converting phage, designated Stx2phi-I, and compared it with three recently reported Stx2-phage genomes. Stx2phi-I consisted of 61,765 bp, which included 166 open reading frames. When compared to 933W, VT2-Sakai and VT2-Sa phages, six characteristic regions (regions I-VI) were found in the Stx2 phage genomes although overall homology was more than 95% between these phages. Stx2phi-I exhibited remarkable differences in these regions as compared with VT-2 Sakai and VT2-Sa genes but not with 933W phage. Characteristic repeat sequences were found in regions I-IV where the genes responsible for the construction of head and tail are located. Regions V and VI, which are the most distinct portion in the entire phage genome were located in the upstream and downstream regions of the Stx2 operons that are responsible for the immunity and replication, and host lysis. These data indicated that Stx2phi-I is less homologous to VT2-Sakai and VT2-Sa phages, despite these three phages being found in the strains isolated at the almost same time in the same geographic region but closely related to 933W phage which was found in the E. coli O157 strain 933W isolated 14 years ago in a different geographic area. 相似文献
975.
Fujita M Seki T Inada H Shimizu K Takahama A Sano T 《Bioorganic & medicinal chemistry letters》2002,12(5):771-774
Compounds 1 or 2 which possess dual-acting PAF antagonist/TxSI in a previous paper were modified and evaluated for the dual-acting activity. It was found that several compounds were potent dual-acting PAF antagonist/TxSI in and ex vivo. 6-(2-Chlorophenyl)-3-[4-[(E/Z)-6-ethoxycarbonyl-1-(3-pyridyl)-1-hexenyl]phenylmethyl]-8,11-dimethyl-2,3,4,5-tetrahydro-8H-pyrido[4',3': 4,5]thieno[3,2-f]triazolo[4,3-a]diazepine (12) is excellent orally dual-acting PAF antagonist/TxSI. 相似文献
976.
Stat3 Controls Cell Movements during Zebrafish Gastrulation 总被引:6,自引:0,他引:6
Yamashita S Miyagi C Carmany-Rampey A Shimizu T Fujii R Schier AF Hirano T 《Developmental cell》2002,2(3):363-375
977.
Yuki Doi Motoyuki Shimizu Tomoya Fujita Akira Nakamura Noboru Takizawa Naoki Takaya 《Applied and environmental microbiology》2014,80(6):1910-1918
We identified the extremely nitrite-tolerant bacterium Achromobacter denitrificans YD35 that can grow in complex medium containing 100 mM nitrite (NO2−) under aerobic conditions. Nitrite induced global proteomic changes and upregulated tricarboxylate (TCA) cycle enzymes as well as antioxidant proteins in YD35. Transposon mutagenesis generated NO2−-hypersensitive mutants of YD35 that had mutations at genes for aconitate hydratase and α-ketoglutarate dehydrogenase in the TCA cycle and a pyruvate dehydrogenase (Pdh) E1 component, indicating the importance of TCA cycle metabolism to NO2− tolerance. A mutant in which the pdh gene cluster was disrupted (Δpdh mutant) could not grow in the presence of 100 mM NO2−. Nitrite decreased the cellular NADH/NAD+ ratio and the cellular ATP level. These defects were more severe in the Δpdh mutant, indicating that Pdh contributes to upregulating cellular NADH and ATP and NO2−-tolerant growth. Exogenous acetate, which generates acetyl coenzyme A and then is metabolized by the TCA cycle, compensated for these defects caused by disruption of the pdh gene cluster and those caused by NO2−. These findings demonstrate a link between NO2− tolerance and pyruvate/acetate metabolism through the TCA cycle. The TCA cycle mechanism in YD35 enhances NADH production, and we consider that this contributes to a novel NO2−-tolerating mechanism in this strain. 相似文献
978.
979.
Hui-Min Qin Akihiro Yamamura Takuya Miyakawa Michihiko Kataoka Takahiro Nagai Nahoko Kitamura Nobuyuki Urano Shintaro Maruoka Jun Ohtsuka Koji Nagata Sakayu Shimizu Masaru Tanokura 《Applied microbiology and biotechnology》2014,98(1):243-249
Conjugated polyketone reductase C2 (CPR-C2) from Candida parapsilosis IFO 0708, identified as a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ketopantoyl lactone reductase, belongs to the aldo-keto reductase superfamily. This enzyme reduces ketopantoyl lactone to d-pantoyl lactone in a strictly stereospecific manner. To elucidate the structural basis of the substrate specificity, we determined the crystal structures of the apo CPR-C2 and CPR-C2/NADPH complex at 1.70 and 1.80 Å resolutions, respectively. CPR-C2 adopted a triose-phosphate isomerase barrel fold at the core of the structure. Binding with the cofactor NADPH induced conformational changes in which Thr27 and Lys28 moved 15 and 5.0 Å, respectively, in the close vicinity of the adenosine 2′-phosphate group of NADPH to form hydrogen bonds. Based on the comparison of the CPR-C2/NADPH structure with 3-α-hydroxysteroid dehydrogenase and mutation analyses, we constructed substrate binding models with ketopantoyl lactone, which provided insight into the substrate specificity by the cofactor-induced structure. The results will be useful for the rational design of CPR-C2 mutants targeted for use in the industrial manufacture of ketopantoyl lactone. 相似文献
980.