全文获取类型
收费全文 | 528篇 |
免费 | 37篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2020年 | 2篇 |
2018年 | 7篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 16篇 |
2014年 | 13篇 |
2013年 | 33篇 |
2012年 | 22篇 |
2011年 | 35篇 |
2010年 | 12篇 |
2009年 | 29篇 |
2008年 | 29篇 |
2007年 | 35篇 |
2006年 | 48篇 |
2005年 | 41篇 |
2004年 | 46篇 |
2003年 | 30篇 |
2002年 | 44篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 6篇 |
1995年 | 7篇 |
1994年 | 10篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 1篇 |
1989年 | 6篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1974年 | 4篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1968年 | 1篇 |
排序方式: 共有565条查询结果,搜索用时 15 毫秒
11.
12.
Shinya Harusawa Koichi Sawada Takuji Magata Hiroki Yoneyama Lisa Araki Yoshihide Usami Kouta Hatano Kouichi Yamamoto Daisuke Yamamoto Atsushi Yamatodani 《Bioorganic & medicinal chemistry letters》2013,23(23):6415-6420
S-Alkyl-N-alkylisothiourea compounds containing various cyclic amines were synthesized in the search for novel nonimidazole histamine H3 receptor (H3R) antagonists. Among them, four N-alkyl S-[3-(piperidin-1-yl)propyl]isothioureas 18, 19, 22, and 23 were found to exhibit potent and selective H3R antagonistic activities against in vitro human H3R, but were inactive against in vitro human H4R. Furthermore, three alkyl homologs 18–20 showed inactivity for histamine release in in vivo rat brain microdialysis, suggesting differences in antagonist affinities between species. In addition, in silico docking studies of N-[4-(4-chlorophenyl)butyl]-S-[3-piperidin-1-yl)propyl]isothiourea 19 and a shorter homolog 17 with human/rat H3Rs revealed that structural differences between the antagonist-docking cavities of rat and human H3Rs were likely caused by the Ala122/Val122 mutation. 相似文献
13.
Takao Takahashi Noriko Yamada Kiichi Iwamoto Yoshihide Shimabayashi Kosaku Izutsu 《Bioscience, biotechnology, and biochemistry》2013,77(1):29-36
The phytohemagglutinin of rice seed has been purified by a sequence of steps involving fractionation with ammonium sulfate and successive chromatography on DEAE-and eMcellulose and finally gel filtration on Bio-Gel P-100. The purified rice seed hemagglutinin was shown to be homogeneous by electrophoresis on polyacrylamide gel and its molecular weight was 10,000, calculated from both the Ve/Vo value of gel filtration on Bio-Gel P-100 and the sum of the individual constituents (amino acids, sugars and metals). In addition to amino acid, the rice seed hemagglutinin contained 26.8% covalently bound carbohydrate which was identified and quantitated by gas chromatography of the acetylated alditols. Glucose was the predominant sugar with lesser amounts of glucosamine, xylose, and mannose also being present. And the rice seed hemagglutinin contained 1 g atom of calcium per molecule. The molecular weight of the rice seed hemagglutinin is smallest compared with some of phytohemagglutinins isolated from leguminous seeds and other plant sources. The rice seed hemagglutinin has the blastogenetic activity for human peripheral lymphocytes as well as Phaseolus vulgaris phytohemagglutinins or concanavalin A, jack bean hemagglutinin. 相似文献
14.
The effect of showdomycin on the syntheses of deoxyribonucleotides from various pyrimidine and purine derivatives was studied in cell-free systems from E. coli.The formations of deoxycytidine phosphates, deoxyuridine phosphates, deoxyguanosine phosphates and deoxyadenosine phosphates from the corresponding ribonucleoside diphosphates were all inhibited by low concentrations of showdomycin. The formation of deoxythymidine phosphates from dUMP was also very susceptible to the antibiotic. These inhibitory actions of showdomycin could be reversed by a sulfhydryl compound (mercaptoethanol) but not by nucleosides, in contrast to a previous finding that the inhibitory action of this antibiotic on the cell growth was reversed by compounds belonging to both of these groups.N-Ethylmaleimide (NEM), a thiol reagent which has a structure related to the aglycone moiety of showdomycin, was also found to be a potent inhibitor of both the reduction of CDP and the methylation of dUMP as showdomycin. A mercurial thiol reagent, p-chloromercuribenzoic acid (PCMB), however, was found to be inactive against the methylation of dUMP although the salvage synthesis of dUMP was inhibited by low concentrations of this reagent.The formations of deoxythymidine phosphates and of deoxyuridine phosphates from their respective pyrimidine bases and a deoxyribosyl donor were quite resistant to showdomycin. 相似文献
15.
Yoshihide Komatsu 《Bioscience, biotechnology, and biochemistry》2013,77(9):1328-1339
14C-Labelled showdomycin was rapidly taken up by Escherichia coli K-12 cells. The showdomycin uptake was highly temperature dependent, sensitive to azide and N-ethyl-maleimide, but was only partially inhibited by treatment with high concentration of iodoacetic acid.The uptake of showdomycin was inhibited by a wide variety of nucleosides but not by purine and pyrimidine bases, nucleotides, ribose or ribose-5-phosphate. The inhibition of showdomycin uptake by adenosine was of a competitive type.Since nucleosides inhibited the uptake of showdomycin but did not facilitate its efflux, they must play a role of inhibitors to the entry of the antibiotic into cells.Removal of extracellular showdomycin by washing, or inhibition of its subsequent entry into cells by the addition of nucleosides or sulfhydryl compounds resulted in a rapid decrease in the intracellular level of the antibiotic during subsequent incubation. 相似文献
16.
Among the syntheses of DNA, RNA and protein in Escherichia coli cells, the DNA synthesis was found to be preferentially inhibited at lower concentrations of showdomycin. At such lower concentrations of this antibiotic, serious decreases in the synthesis of deoxycytidine phosphates and in de novo synthesis of deoxythymidine phosphates were found in parallel with the decrease in the synthesis of DNA, although the syntheses of other pyrimidine nucleotides were not significantly diminished. The salvage synthesis of deoxythymidine phosphates was very resistant to this antibiotic. The inhibitory action of this antibiotic on DNA synthesis could be reversed by the concomitant addition of a thiol compound or a nucleoside. When a nucleoside was added after the completion of the inhibition by showdomycin, the recovery of the DNA synthesis from the inhibition was detected only after the recovery of the syntheses of pyrimidine ribotides, pyrimidine deoxyribotides and RNA have become distinct. 相似文献
17.
Yoshihide Shimabayashi Takao Takahashi Kiichi Iwamoto 《Bioscience, biotechnology, and biochemistry》2013,77(12):1673-1681
The devised method consists of the enzymatic hydrolysis, separation of deoxyribosides in the hydrolysate by paper chromatography and paper electrophoresis, and the estimation of the separated fractions with L. leichmannii. This method permits the determination of deoxyriboside composition of the smaller amounts of DNA or the related compounds with relatively higher accuracy even under the presence of some other compounds when nucleic acids and acid insoluble fractions of the chick embryo were analyzed.The change of each deoxyriboside composition in acid insoluble fraction prepared from the 3 to 19 day old embryos investigated by the method. Among the major four deoxyribosides, the contents of deoxyguanosine and of deoxycytidine was nearly constant during the development of the embryo, whereas that of thymidine and of deoxyadenosine appeared to undergo the change slightly at the periods from 10 to 15 days incubation. It seems that this periods is also the most active time of the synthesis of DNA and of the changes of deoxyribosyl compounds in acid soluble fraction through the embryo growth. 相似文献
18.
Yasumasa Kimura Takahiro Soma Naoko Kasahara Diane Delobel Takeshi Hanami Yuki Tanaka Michiel J. L. de Hoon Yoshihide Hayashizaki Kengo Usui Matthias Harbers 《PloS one》2016,11(2)
Analytical PCR experiments preferably use internal probes for monitoring the amplification reaction and specific detection of the amplicon. Such internal probes have to be designed in close context with the amplification primers, and may require additional considerations for the detection of genetic variations. Here we describe Edesign, a new online and stand-alone tool for designing sets of PCR primers together with an internal probe for conducting quantitative real-time PCR (qPCR) and genotypic experiments. Edesign can be used for selecting standard DNA oligonucleotides like for instance TaqMan probes, but has been further extended with new functions and enhanced design features for Eprobes. Eprobes, with their single thiazole orange-labelled nucleotide, allow for highly sensitive genotypic assays because of their higher DNA binding affinity as compared to standard DNA oligonucleotides. Using new thermodynamic parameters, Edesign considers unique features of Eprobes during primer and probe design for establishing qPCR experiments and genotyping by melting curve analysis. Additional functions in Edesign allow probe design for effective discrimination between wild-type sequences and genetic variations either using standard DNA oligonucleotides or Eprobes. Edesign can be freely accessed online at http://www.dnaform.com/edesign2/, and the source code is available for download. 相似文献
19.
Rapid SNP diagnostics using asymmetric isothermal amplification and a new mismatch-suppression technology 总被引:2,自引:0,他引:2
Mitani Y Lezhava A Kawai Y Kikuchi T Oguchi-Katayama A Kogo Y Itoh M Miyagi T Takakura H Hoshi K Kato C Arakawa T Shibata K Fukui K Masui R Kuramitsu S Kiyotani K Chalk A Tsunekawa K Murakami M Kamataki T Oka T Shimada H Cizdziel PE Hayashizaki Y 《Nature methods》2007,4(3):257-262
We developed a rapid single nucleotide polymorphism (SNP) detection system named smart amplification process version 2 (SMAP 2). Because DNA amplification only occurred with a perfect primer match, amplification alone was sufficient to identify the target allele. To achieve the requisite fidelity to support this claim, we used two new and complementary approaches to suppress exponential background DNA amplification that resulted from mispriming events. SMAP 2 is isothermal and achieved SNP detection from whole human blood in 30 min when performed with a new DNA polymerase that was cloned and isolated from Alicyclobacillus acidocaldarius (Aac pol). Furthermore, to assist the scientific community in configuring SMAP 2 assays, we developed software specific for SMAP 2 primer design. With these new tools, a high-precision and rapid DNA amplification technology becomes available to aid in pharmacogenomic research and molecular-diagnostics applications. 相似文献
20.
Takafumi Ito Hisashi Murata Yoshihide Yasui Morimasa Matsui Tadashi Sakai Kiyoshi Yamauchi 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1995,667(2)
An high-performance liquid chromatographic method with post-column derivatization has been developed for the simultaneous determination of ascorbic acid (AA) and dehydroascorbic acid (DHAA) in fish tissues. Extracted AA and DHAA were separated by a Shim-pack SCR-101H column within 20 min, reacted with sodium hydroxide containing sodium borohydride and monitored at 300 nm. The detection limits for both AA and DHAA were 0.1 μg/ml. 相似文献