全文获取类型
收费全文 | 214篇 |
免费 | 16篇 |
专业分类
230篇 |
出版年
2021年 | 2篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 2篇 |
2015年 | 4篇 |
2014年 | 8篇 |
2013年 | 7篇 |
2012年 | 5篇 |
2011年 | 4篇 |
2010年 | 9篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 4篇 |
2006年 | 1篇 |
2005年 | 3篇 |
2004年 | 8篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 9篇 |
2000年 | 4篇 |
1999年 | 12篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1986年 | 7篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 8篇 |
1980年 | 1篇 |
1979年 | 11篇 |
1978年 | 11篇 |
1977年 | 4篇 |
1975年 | 2篇 |
1974年 | 7篇 |
1973年 | 1篇 |
1969年 | 2篇 |
1958年 | 1篇 |
1931年 | 1篇 |
1928年 | 3篇 |
排序方式: 共有230条查询结果,搜索用时 15 毫秒
121.
122.
Phe161 and Arg166 of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens belong to a newly discovered sequence motif in flavoprotein hydroxylases with a putative dual function in FAD and NADPH binding [1]. To study their role in more detail, Phe161 and Arg166 were selectively changed by site-directed mutagenesis. F161A and F161G are catalytically competent enzymes having a rather poor affinity for NADPH. The catalytic properties of R166K are similar to those of the native enzyme. R166S and R166E show impaired NADPH binding and R166E has lost the ability to bind FAD. The crystal structure of substrate complexed F161A at 2.2 A is indistinguishable from the native enzyme, except for small changes at the site of mutation. The crystal structure of substrate complexed R166S at 2.0 A revealed that Arg166 is important for providing an intimate contact between the FAD binding domain and a long excursion of the substrate binding domain. It is proposed that this interaction is essential for structural stability and for the recognition of the pyrophosphate moiety of NADPH. 相似文献
123.
124.
Rob Noorlag Pauline MW van Kempen Cathy B Moelans Rick de Jong Laura ER Blok Ronald Koole Wilko Grolman Paul J van Diest Robert JJ van Es Stefan M Willems 《Epigenetics》2014,9(9):1220-1227
Silencing of tumor suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis and a potential target for personalized cancer treatment. In head and neck cancer, little is known about the role of promoter hypermethylation in survival. Using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) we investigated the role of promoter hypermethylation of 24 well-described genes (some of which are classic TSGs), which are frequently methylated in different cancer types, in 166 HPV-negative early oral squamous cell carcinomas (OSCC), and 51 HPV-negative early oropharyngeal squamous cell carcinomas (OPSCC) in relation to clinicopathological features and survival. Early OSCC showed frequent promoter hypermethylation in RARB (31% of cases), CHFR (20%), CDH13 (13%), DAPK1 (12%), and APC (10%). More hypermethylation (≥ 2 genes) independently correlated with improved disease specific survival (hazard ratio 0.17, P = 0.014) in early OSCC and could therefore be used as prognostic biomarker. Early OPSCCs showed more hypermethylation of CDH13 (58%), TP73 (14%), and total hypermethylated genes. Hypermethylation of two or more genes has a significantly different effect on survival in OPSCC compared with OSCC, with a trend toward worse instead of better survival. This could have a biological explanation, which deserves further investigation and could possibly lead to more stratified treatment in the future. 相似文献
125.
Crustacean and cheliceratan hemocyanins (oxygen-transport proteins) and
insect hexamerins (storage proteins) are homologous gene products, although
the latter do not bind oxygen and do not possess the copper- binding
histidines present in the hemocyanins. An alignment of 19 amino acid
sequences of hemocyanin subunits and insect hexamerins was made, based on
the conservation of elements of secondary structure observed in X-ray
structures of two hemocyanin subunits. The alignment was analyzed using
parsimony and neighbor-joining methods. Results provide strong indications
for grouping together the sequences of the 2 crustacean hemocyanin
subunits, the 5 cheliceratan hemocyanin subunits, and the 12 insect
hexamerins. Within the insect clade, four methionine- rich proteins, four
arylphorins, and two juvenile hormone-suppressible proteins from
Lepidoptera, as well as two dipteran proteins, form four separate groups.
In the absence of an outgroup sequence, it is not possible to present
information about the ancestral state from which these proteins are
derived. Although this family of proteins clearly consists of homologous
gene products, there remain striking differences in gene organization and
site of biosynthesis of the proteins within the cell. Because studies on
18S and 12S rRNA sequences indicate a rather close relationship between
insects and crustaceans, we propose that hemocyanin is the ancestral
arthropod protein and that insect hexamerins lost their copper-binding
capability after divergence of the insects from the crustaceans.
相似文献
126.
127.
R E Bontrop G M Schreuder D G Elferink M M Mikulski R Geerse M J Giphart 《Journal of immunology (Baltimore, Md. : 1950)》1986,137(1):211-216
During routine typing procedures the individual GER was demonstrated to possess an unusual class II phenotype exhibiting three DR serotypes (DR1, DR2, DRw6). Closer serologic examination on this person's family showed that the DR1 and DR2 antigens segregated together on one haplotype. Biochemical evidence will be presented that the B cell line derived from the individual GER expresses five distinct types of DR molecules. Antigen presentation studies proved that the DR molecules carrying either DR1, DR2, or DRw6 (DRw13) allodeterminants are not only coordinately expressed but also are functional. No evidence could be found for altered DQ expression. The implications of these findings for the evolutionary aspects of the MHC class II region will be discussed. 相似文献
128.
129.
Gary A. Flynn Ann L. Akeson Ram Dharanipragada Michael J. Genin J. Antony Malikayil Richard Pottorf Jeffery S. Sabol Herman Schreuder Ron Tomlinson Phil Waid Ron Barrett Jeff Jacobs Steve Yanofsky 《International journal of peptide research and therapeutics》1998,5(2-3):93-100
Summary A collection of complementary peptide caricatures that closely mimic low-energy (presumably highly populated) conformations
of amino acids of interest would constitute a valuable tool set to study the interactions of small peptide ligands with their
biological targets. Our general strategy for the design, synthesis and application of peptidomimetics is presented. An illustration
of how structural information from mimetics combined with cutting edge biophysical data can be used to derive a model for
the bound conformation of an 11-mer peptide antagonist with the IL-1 receptor is given. 相似文献
130.
Elmar W Tobi Bastiaan T Heijmans Dennis Kremer Hein Putter Henriette A Delemarre-van de Waal Martijn JJ Finken Jan M Wit P Eline Slagboom 《Epigenetics》2011,6(2):171-176
Being born small for gestational age (SGA), a proxy for intrauterine growth restriction (IUGR) and prenatal famine exposure are both associated with a greater risk of metabolic disease. Both associations have been hypothesized to involve epigenetic mechanisms. We investigated whether prenatal growth restriction early in pregnancy was associated with changes in DNA methylation at loci that were previously shown to be sensitive to early gestational famine exposure. We compared 38 individuals born preterm (<32 weeks) and with a birth weight too low for their gestational age (less than −1SDS; SGA) with 75 individuals born preterm but with a birth weight appropriate for their gestational age (greater than −1SDS) and a normal postnatal growth (greater than −1SDS at three months post term; AGA). The SGA individuals were not only lighter at birth, but also had a smaller length (p = 3.3 × 10−13) and head circumference at birth (p = 4.1 × 10−13). The DNA methylation levels of IGF2, GNASAS, INSIGF and LEP were 48.5, 47.5, 79.4 and 25.7% respectively. This was not significantly different between SGA and AGA individuals. Risk factors for being born SGA, including preeclampsia and maternal smoking, were also not associated with DNA methylation at these loci. Growth restriction early in development is not associated with DNA methylation at loci shown to be affected by prenatal famine exposure. Our and previous results by others indicate that prenatal growth restriction and famine exposure may be associated with different epigenetic changes or non-epigenetic mechanisms that may lead to similar later health outcomes.Key words: SGA, DOHAD, IUGR, DNA methylation, famine, IGF2, LEP, INS, GNASAS 相似文献