全文获取类型
收费全文 | 2023篇 |
免费 | 130篇 |
国内免费 | 1篇 |
出版年
2021年 | 23篇 |
2020年 | 12篇 |
2019年 | 12篇 |
2018年 | 31篇 |
2017年 | 17篇 |
2016年 | 37篇 |
2015年 | 32篇 |
2014年 | 56篇 |
2013年 | 115篇 |
2012年 | 90篇 |
2011年 | 111篇 |
2010年 | 55篇 |
2009年 | 53篇 |
2008年 | 92篇 |
2007年 | 91篇 |
2006年 | 104篇 |
2005年 | 87篇 |
2004年 | 106篇 |
2003年 | 79篇 |
2002年 | 81篇 |
2001年 | 77篇 |
2000年 | 62篇 |
1999年 | 69篇 |
1998年 | 21篇 |
1997年 | 20篇 |
1996年 | 14篇 |
1995年 | 20篇 |
1994年 | 18篇 |
1993年 | 18篇 |
1992年 | 48篇 |
1991年 | 38篇 |
1990年 | 40篇 |
1989年 | 30篇 |
1988年 | 58篇 |
1987年 | 44篇 |
1986年 | 18篇 |
1985年 | 26篇 |
1984年 | 23篇 |
1983年 | 23篇 |
1982年 | 12篇 |
1979年 | 16篇 |
1978年 | 19篇 |
1977年 | 11篇 |
1976年 | 13篇 |
1975年 | 13篇 |
1974年 | 17篇 |
1973年 | 17篇 |
1972年 | 10篇 |
1970年 | 9篇 |
1969年 | 17篇 |
排序方式: 共有2154条查询结果,搜索用时 656 毫秒
101.
Hiroaki Kamachi Keisuke Tanaka Ryo C. Yanagita Akira Murakami Kazuma Murakami Harukuni Tokuda Nobutaka Suzuki Yu Nakagawa Kazuhiro Irie 《Bioorganic & medicinal chemistry》2013,21(10):2695-2702
We have recently developed a simplified analog of aplysiatoxin (aplog-1) as an activator of protein kinase C (PKC) with anti-proliferative activity like bryostain 1. To identify sites in aplog-1 that could be readily modified to optimize therapeutic performance and to develop a molecular probe for examining the analog’s mode of action, substituent effects on the phenol ring were systematically examined. Whereas hydrophilic acetamido derivatives were less active than aplog-1 in inhibiting cancer cell growth and binding to PKCδ, introduction of hydrophobic bromine and iodine atoms enhanced both biological activities. The anti-proliferative activity was found to correlate closely with molecular hydrophobicity, and maximal activity was observed at a log P value of 4.0–4.5. On the other hand, an induction test with Epstein–Barr virus early antigen demonstrated that these derivatives have less tumor-promoting activity in vitro than aplog-1 regardless of the hydrophobicity of their substituents. These results would facilitate rapid preparation of molecular probes to examine the mechanism of the unique biological activities of aplog-1. 相似文献
102.
Yuji Nakamura Teppei Fujimoto Yasuyuki Ogawa Hidenori Namiki Sayaka Suzuki Masayoshi Asano Chie Sugita Akiyoshi Mochizuki Shojiro Miyazaki Kazuhiko Tamaki Yoko Nagai Shin-ichi Inoue Takahiro Nagayama Mikio Kato Katsuyoshi Chiba Kiyoshi Takasuna Takahide Nishi 《Bioorganic & medicinal chemistry》2013,21(11):3175-3196
With the aim to address an undesired cardiac issue observed with our related compound in the recently disclosed novel series of renin inhibitors, further chemical modifications of this series were performed. Extensive structure–activity relationships studies as well as in vivo cardiac studies using the electrophysiology rat model led to the discovery of clinical candidate trans-adamantan-1-ol analogue 56 (DS-8108b) as a potent renin inhibitor with reduced potential cardiac risk. Oral administration of single doses of 3 and 10 mg/kg of 56 in cynomolgus monkeys pre-treated with furosemide led to significant reduction of mean arterial blood pressure for more than 12 h. 相似文献
103.
Masao Fujimoto Akira Kuninaka Hiroshi Yoshino 《Bioscience, biotechnology, and biochemistry》2013,77(9):1555-1561
Nuclease P1 cleaved substantially all phosphodiester bonds in rRNA, tRNA, poly(I), poly(U), poly(A), poly(C), poly(G), poly(I)·poly(C), native DNA and heat-denatured DNA to produce exclusively 5′-mononucleotides. Single-stranded polynucleotides were much more susceptible than double-stranded ones. Influence of pH and ionic strength on the hydrolysis rate significantly varied with the kind of polynucleotides. The enzyme also hydrolyzed 3′-phosphomonoester bonds in 3′-AMP, 3′-GMP, 3′-UMP, 3′-CMP, 3′-dAMP, 3′-dGMP, 3′-dCMP and 3′-dTMP. Ribonucleoside 3′-monophosphates were hydrolyzed 20 to 50 times faster than the corresponding 3′-deoxyribonucleotides. Base preference of the enzyme for 3′-ribonucleotides was in the order of G>A>C≧U, whereas that for 3′-deoxyribo-nucleotides was in the order of C≧T>A≧G. The 3′-phosphomonoester bonds in nucleoside 3′, 5′-diphosphates, coenzyme A and dinucleotides bearing 3′-phosphate were hydrolyzed at a rate similar to that for the corresponding 3′-mononucleotides. Adenosine 2′-monophosphate was highly resistant, being split at less than 1/3,000 the rate at which 3′-AMP was split. 相似文献
104.
Masakazu Miyakado Nobuo Ohno Yoshitoshi Okuno Masachika Hirano Keimei Fujimoto Hirosuke Yoshioka 《Bioscience, biotechnology, and biochemistry》2013,77(1):267-272
In connection with disclosure of a new class of insecticides, the modified phenylacetates, six new optically active α-isopropy-4-substituted phenylacetic acids whose substituents are respectively 4-methyl,4-methoxy, 4-fluoro, 4-chloro, 4-bromo and 3,4-methylenedioxy group were prepared by optical resolution and their absolute configurations were determined by comparative ORD with α-isopropylphenylacetic acid derivatives whose absolute configuration is known as (S)-(²). Esters of the (S)-(²)-acids with 5-benzyl-3-furylmethanol were nearly twice toxic to Musca domestica than those of the racemic esters. Optical purities of the resolved acids were determined by GLC and NMR (with Eu-FOD) as (?)-methyl esters. 相似文献
105.
Masao Fujimoto Akira Kuninaka Hiroshi Yoshino 《Bioscience, biotechnology, and biochemistry》2013,77(10):1991-1997
The inhibitory action of compressed hydrocarbon gases on the growth of the yeast Saccharomyces cerevisiae was investigated quantitatively by microcalorimetry. Both the 50% inhibitory pressure (IP50) and the minimum inhibitory pressure (MIP), which are regarded as indices of the toxicity of hydrocarbon gases, were determined from growth thermograms. Based on these values, the inhibitory potency of the hydrocarbon gases increased in the order methane << ethane < propane < i-butane < n-butane. The toxicity of these hydrocarbon gases correlated to their hydrophobicity, suggesting that hydrocarbon gases interact with some hydrophobic regions of the cell membrane. In support of this, we found that UV absorbing materials at 260 nm were released from yeast cells exposed to compressed hydrocarbon gases. Additionally, scanning electron microscopy indicated that morphological changes occurred in these cells. 相似文献
106.
Motoo MotooShibata Masaru Uyeda Yutaka Kido Yuki Fujimoto Yuji Takano Yukie Yoshioka 《Bioscience, biotechnology, and biochemistry》2013,77(12):3377-3382
Streptomyces sp. No. B-1625, which was identified as a strain of Streptomyces antibioticus, is a typical producer of actinomycin, but also produces minor acidic antibiotic components (FA), besides actinomycins X2, D and X0β. The FA-components, which were obtained with a high-producing mutant, 11M-21, showed antibacterial and antitumor activities, and also similar visible and UV absorption spectra to those characteristic of actinomycin. The FA-components were separated into five components, FA1 FA2α, FA2β, FA3α and FA3β, on TLC. Among them, one component, FA3β, isolated in a purified state as an orange powder, has a composition of C, 52.97: H, 6.34: N, 10.48%, and is active against B. subtilis at a MIC of 5mcg/ml. The FA3β component showed pKa′ of 5.4 and 12.0 and λmax at 443, 427 and 233 nm. From these properties, FA3β is considered to be an acidic actinomycin congener. 相似文献
107.
Akira Kuninaka Masao Fujimoto Hiroshi Yoshino 《Bioscience, biotechnology, and biochemistry》2013,77(3):603-610
Sixteen 2′→5′ dinucleotides; (2′–5′)pA-A, pA-G, pA-C, pA-U, pG-A, pG-G, pG-C, pG-U, pC-A, pC-G, pC-C, pC-U, pU-A, pU-G, pU-C, and pU-U were detected in nuclease P1 digest of a technical grade yeast RNA by means of gel filtration on Sephadex G-10, DEAE-Sephadex A-25 column chromatography in the presence of 7 m urea, paper electrophoresis and paper chromatography. Content of each dinucleotide was about 0.1 to 0.6% of the digest. As the sixteen 2′→5′ dinucleotides were found in all of the digests of technical grade RNA preparations tested, each polynucleotide chain in the preparations may be concluded to contain several per cent of the 2′–5′ minor phosphodiester linkages in addition to the 3′–5′ major phosphodiester linkages. 相似文献
108.
Masao Fujimoto Akira Kuninaka Hiroshi Yoshino 《Bioscience, biotechnology, and biochemistry》2013,77(7):1111-1119
Nuclease P1 from Penicillium citrinum was found to be produced in a form of complex with malonogalactan (a galactan, 1, 5-β-galactofuranoside polymer esterfied with malonic acid at position 3) in the culture on wheat bran. Neither nuclease P1-malonogalactan complex nor malonogalactan was produced in a liquid medium. Nuclease P1-malonogalactan complexes, P1-MG I, II, and III were purified from an aqueous extract of the culture on wheat bran. The most anionic complex, P1-MG III, was composed of the protein, carbohydrate and malonic acid in the ratio of 1: 2.6: 0.5 (w/w). The complex was not dissociated by purification procedures including fractionations with acetone and ammonium sulfate, gel filtration and DEAE-cellulose chromatography. A malonogalactan-specific carboxylesterase was found in culture of the same mold on wheat bran. Nuclease P1-malonogalactan was demalonylated by the esterase to yield nuclease P1-galactan. The binding of nuclease P1 to galactan was rather loose so that nuclease P1-galactan complex was partially dissociated by DEAE-cellulose chromatography. Attempt to reconstitute the complex from nuclease P1 and malonogalactan upon mixing was unsuccessful. Exogenously supplemented nuclease P1 did not associate with malonogalactan in the growing culture on wheat bran, either.Several extracellular enzymes such as RNase, β-galactosidase and protease were also found in a form of complex with malonogalactan in the culture on wheat bran. 相似文献
109.
Kazuma?Takahashi Takashi?Kondo Yasunaga?Yoshikawa Kiyotaka?Watanabe Koichi?OrinoEmail author 《Acta veterinaria Scandinavica》2013,55(1):70
Background
Horse fibrinogen has been identified as a plasma specific ferritin-binding protein. There are two ways in the binding of ferritin-binding protein with ferritin: one is direct binding and the other is indirect binding which is heme-mediated. The aim of this study was to analyze the binding between horse fibrinogen and ferritin.Findings
Although fibrinogen in horse plasma did not show the binding to ferritin coated on the plate wells, after following heat-treatment (60°C, 30 min) of horse plasma, plasma fibrinogen as well as purified horse fibrinogen bound to plates coated with horse spleen ferritin, but not with its apoferritin which lost heme as well as iron after the treatment of reducing reagent. Binding of purified or plasma fibrinogen to ferritin was inhibited by hemin and Sn-protoporphyrin IX (Sn-PPIX), but not by PPIX or Zn-PPIX.Conclusions
Heat-treatment of horse plasma enabled plasma fibrinogen to bind to plate well coated with holo-ferritin. From the binding analysis of fibrinogen and ferritin, it is suggested that horse fibrinogen recognized iron or tin in complexed with the heme- or the hemin-ring, and also suggest that some fibrinogens circulate in the form of a complex with ferritin and/or heat-labile factors which inhibit the binding of fibrinogen with ferritin.110.
Hitomi Ueno Hajime Okita Shingo Akimoto Kenichiro Kobayashi Kazuhiko Nakabayashi Kenichiro Hata Junichiro Fujimoto Jun-ichi Hata Masahiro Fukuzawa Nobutaka Kiyokawa 《PloS one》2013,8(4)
A number of specific, distinct neoplastic entities occur in the pediatric kidney, including Wilms’ tumor, clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), rhabdoid tumor of the kidney (RTK), and the Ewing’s sarcoma family of tumors (ESFT). By employing DNA methylation profiling using Illumina Infinium HumanMethylation27, we analyzed the epigenetic characteristics of the sarcomas including CCSK, RTK, and ESFT in comparison with those of the non-neoplastic kidney (NK), and these tumors exhibited distinct DNA methylation profiles in a tumor-type-specific manner. CCSK is the most frequently hypermethylated, but least frequently hypomethylated, at CpG sites among these sarcomas, and exhibited 490 hypermethylated and 46 hypomethylated CpG sites in compared with NK. We further validated the results by MassARRAY, and revealed that a combination of four genes was sufficient for the DNA methylation profile-based differentiation of these tumors by clustering analysis. Furthermore, THBS1 CpG sites were found to be specifically hypermethylated in CCSK and, thus, the DNA methylation status of these THBS1 sites alone was sufficient for the distinction of CCSK from other pediatric renal tumors, including Wilms’ tumor and CMN. Moreover, combined bisulfite restriction analysis could be applied for the detection of hypermethylation of a THBS1 CpG site. Besides the biological significance in the pathogenesis, the DNA methylation profile should be useful for the differential diagnosis of pediatric renal tumors. 相似文献