全文获取类型
收费全文 | 479篇 |
免费 | 25篇 |
专业分类
504篇 |
出版年
2023年 | 1篇 |
2021年 | 12篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 6篇 |
2016年 | 13篇 |
2015年 | 21篇 |
2014年 | 25篇 |
2013年 | 39篇 |
2012年 | 44篇 |
2011年 | 34篇 |
2010年 | 14篇 |
2009年 | 20篇 |
2008年 | 29篇 |
2007年 | 22篇 |
2006年 | 26篇 |
2005年 | 18篇 |
2004年 | 15篇 |
2003年 | 24篇 |
2002年 | 20篇 |
2001年 | 7篇 |
2000年 | 11篇 |
1999年 | 10篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有504条查询结果,搜索用时 15 毫秒
431.
Molecular adaptation at low temperature requires specificities represented mainly by modifications in the gene sequence and consequently in the protein primary structure. To characterize the molecular mechanisms responsible for ribosome cold-adaptation, we compared the ribosomal P0 and P2 genes from the Antarctic ciliate Euplotes focardii with homologous genes from mesophilic organisms, including the ciliates Tetrahymena thermophila and non cold-adapted Euplotes species. This analysis revealed the presence of non synonymous mutations unique to E. focardii. In the P0 protein the mutations produced amino acid substitutions that increased the molecular flexibility that may facilitate a conformational adjustment associated with the interaction with the GTPase center of the large subunit rRNA, and increased the hydrophobicity of the region involved in the interaction with P1/P2 heterodimer, probably to keep associated the ribosomal stalk in the cold. In the P2 protein the mutations produced amino acid substitutions that increased the N-terminus flexibility, which may facilitate interactions with P1 protein in the formation of the heterodimer, and reduced the mobility of the C-terminus, to stabilize the stalk during ribosomal activity. Finally, P proteins appeared to be valid markers for investigating the phylogenetic origin of early eukaryotes. 相似文献
432.
433.
434.
435.
Computational identification of protein coding potential of conserved sequence tags through cross-species evolutionary analysis 总被引:4,自引:0,他引:4
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
The identification of conserved sequence tags (CSTs) through comparative genome analysis may reveal important regulatory elements involved in shaping the spatio-temporal expression of genetic information. It is well known that the most significant fraction of CSTs observed in human–mouse comparisons correspond to protein coding exons, due to their strong evolutionary constraints. As we still do not know the complete gene inventory of the human and mouse genomes it is of the utmost importance to establish if detected conserved sequences are genes or not. We propose here a simple algorithm that, based on the observation of the specific evolutionary dynamics of coding sequences, efficiently discriminates between coding and non-coding CSTs. The application of this method may help the validation of predicted genes, the prediction of alternative splicing patterns in known and unknown genes and the definition of a dictionary of non-coding regulatory elements. 相似文献
436.
Lolli G Thaler F Valsasina B Roletto F Knapp S Uggeri M Bachi A Matafora V Storici P Stewart A Kalisz HM Isacchi A 《Proteomics》2003,3(7):1287-1298
An inhibitor affinity chromatography (IAC) method has been developed for the analysis of inhibitor-protein interactions as a complementary approach to two-dimensional electrophoresis for functional proteomics studies. The procedure was developed utilizing a cyclin-dependent kinase 2 (Cdk2) inhibitor coupled to a polymeric resin and validated using a number of proteins interacting with the inhibitor with different specificities. Cdk2 and the other kinases bound and eluted from the resin in accordance with the relative in vitro potency of the inhibitor for each enzyme. Molecular interactions with the Cdk2 inhibitor were compared for HCT116 cancer cells versus rat pancreatic acinar cells. Proteins interacting with the ligand on the IAC matrix were identified by mass spectrometry. Isothermal calorimetry was used to confirm and quantitatively evaluate the binding affinity of some of the interacting proteins. Heat-shock protein (Hsp) 70 and Hsp27 were the strongest interactors with the inhibitor, displaying binding affinities comparable to those of Cdk2. These results support the use of IAC as a general method for the rapid identification and qualitative evaluation of the in vivo targets and potential side effects of a given drug. 相似文献
437.
438.
Alotto D Ariotti S Graziano S Verrua R Stella M Magliacani G Castagnoli C 《Cell and tissue banking》2002,3(1):3-10
New surgical procedures requiring viable skin have increased rapidly over the last few years. The cell viability assessment
in allograft skin is a major step forward in burn treatment, since it is well-known that taking is correlated with grafted
tissue viability. Various methods, both qualitative and quantitative, are currently used. Although qualitative assays (histomorphology,
immunocytochemistry) are routinely performed in our laboratory, there arose a need to set up a standardised quantitative assay
in an attempt to obtain a cut-off value so that the skin sample could be determined valid or not for grafting. Therefore,
two different tetrazolium salt compounds MTT and WST-1, were compared in order to determine their efficacy in the evaluation
of tissue viability. Several experimental conditions were analysed: 1- cellular cultures of keratinocytes and fibroblasts,
2- fresh skin tissue samples, 3- the same specimen tested daily for at least 2 weeks, 4- after cryopreservation and thawing.
Viable cells were analysed by the cleavage of tetrazolium salts to formazan by cellular enzymes. The formazan dye produced
by metabolically active cells was then quantified by measuring the absorbance of the dye solution at the appropriate wavelength.
It was seen that WST-1 is easier to handle, more stable, has a wider line arrange, accelerated colour development and is more
sensitive than MTT on fresh specimens and cell suspension. However, after 72 hours of storage at 4°C, most of the WST-1 tested
specimens no longer gave any absorbance signal, whilst MTT specimens were seen to give a signal for more than two weeks. Moreover,
after thawing WST-1 tested samples were almost negative,whilst MTT samples continued to give strong signals. In conclusion,
WST-1 assay offers rapid and precise results as to the cell viability of fresh allografts and cell cultures, whilst the MTT
method is much more useful in establishing viability after long conservation and cryopreservation. In our clinical experience,
allografts
transplanted at 72 hr post-harvesting or after cryopreservation showed a mean of take more than of 80%, demonstrating that
the MTT system is more reliable for the determination of allograft viability. Studies are ongoing with larger clinical cohorts
to establish the precise cut-off value for skin graft validation.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
439.
A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Duan QL Nikpoor B Dube MP Molinaro G Meijer IA Dion P Rochefort D Saint-Onge J Flury L Brown NJ Gainer JV Rouleau JL Agostoni A Cugno M Simon P Clavel P Potier J Wehbe B Benarbia S Marc-Aurele J Chanard J Foroud T Adam A Rouleau GA 《American journal of human genetics》2005,77(4):617-626
Angiotensin I-converting enzyme inhibitors (ACEi), which are used to treat common cardiovascular diseases, are associated with a potentially life-threatening adverse reaction known as angioedema (AE-ACEi). We have previously documented a significant association between AE-ACEi and low plasma aminopeptidase P (APP) activity. With eight large pedigrees, we hereby demonstrate that this quantitative trait is partially regulated by genetic factors. We tested APP activity using a variance-component QTL analysis of a 10-cM genomewide microsatellite scan enriched with seven markers over two candidate regions. We found significant linkage (LOD = 3.75) to a locus that includes the XPNPEP2 candidate gene encoding membrane-bound APP. Mutation screening of this QTL identified a large coding deletion segregating in one pedigree and an upstream single-nucleotide polymorphism (C-2399A SNP), which segregates in the remaining seven pedigrees. Measured genotype analysis strongly suggests that the linkage signal for APP activity at this locus is accounted for predominantly by the SNP association. In a separate case-control study (20 cases and 60 controls), we found significant association of this SNP to ACEi-induced AE (P=.0364). In conclusion, our findings provide supporting evidence that the C-2399A variant in XPNPEP2 is associated with reduced APP activity and a higher incidence of AE-ACEi. 相似文献
440.
Sso7d is a 62-residue protein from the hyperthemophilic archaeon Sulfolobus solfataricus with a denaturation temperature close to 100 degrees C around neutral pH. An engineered form of Sso7d truncated at leucine 54 (L54Delta) is significantly less stable, with a denaturation temperature of 53 degrees C. Molecular dynamics (MD) studies of Sso7d and its truncated form at two different temperatures have been performed. The results of the MD simulations at 300 K indicate that: (1) the flexibility of Sso7d chain at 300 K agrees with that detected from X-ray and NMR structural studies; (2) L54Delta remains stable in the native folded conformation and possesses an overall dynamic behavior similar to that of the parent protein. MD simulations performed at 500 K, 10 ns long, indicate that, while Sso7d is in-silico resistant to high temperature, the truncated variant partially unfolds, revealing the early phases of the thermal unfolding pathway of the protein. Analysis of the trajectories of L54Delta suggests that the unzipping of the N-terminal and C-terminal beta-strands should be the first event of the unfolding pathway, and points out the regions more resistant to thermal unfolding. These findings allow one to understand the role played by specific interactions connecting the two ends of the chain for the high thermal stability of Sso7d, and support recent hypotheses on its folding mechanism emerged from site-directed mutagenesis studies. 相似文献