全文获取类型
收费全文 | 256篇 |
免费 | 40篇 |
出版年
2022年 | 4篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 16篇 |
2013年 | 13篇 |
2012年 | 6篇 |
2011年 | 15篇 |
2010年 | 4篇 |
2009年 | 7篇 |
2008年 | 11篇 |
2007年 | 6篇 |
2006年 | 8篇 |
2005年 | 6篇 |
2004年 | 10篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 5篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1994年 | 3篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 9篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1970年 | 4篇 |
1969年 | 2篇 |
1966年 | 3篇 |
1962年 | 2篇 |
1903年 | 1篇 |
排序方式: 共有296条查询结果,搜索用时 15 毫秒
101.
Tranchant I Hervé AC Carlisle S Lowe P Slevin CJ Forssten C Dilleen J Tabor AB Williams DE Hailes HC 《Bioconjugate chemistry》2007,18(1):199-208
The development of electrochemical probes useful for investigating the occupancy by other molecules of sites on complex proteins such as human serum albumin (HSA) is described. Ferrocenyl-(oxoethylene)-fatty acid compounds of different fatty acid chain length probed different binding sites on HSA. The interaction could be changed from one primarily with a drug binding site, when the probe was ferrocene methanol, to one predominantly with medium-chain fatty acid binding sites, by adding an (oxoethylene)-fatty acid substituents. Finally, the interaction could be changed to one interacting primarily with high-affinity long-chain fatty acid binding sites, as the fatty acid chain length in ferrocene-(oxoethylene)-fatty acid molecules increased. These results strongly implied that the binding could be further tailored by relatively simple modifications to the probe, for example, by changing the balance of hydrophobicity and hydrophilicity. The possibility of a procedure using mass-produced electrochemical cells to determine the fractional occupancy of different sites on HSA is demonstrated. 相似文献
102.
Friðgeir Grímsson Bonnie F. Jacobs Johan L. C. H. Van Valkenburg Jan J. Wieringa Alexandros Xafis Neil Tabor 《Grana》2019,58(2):81-98
The palm family, Arecaceae, is notoriously depauperate in Africa today, and its evolutionary, paleobiogeographic, and extinction history there are not well documented by fossils. In this article we report the pollen of two new extinct species of the small genus, Sclerosperma (Arecoideae), from a late Oligocene (27–28 Ma) stratum exposed along the Guang River in Chilga Wereda of north-western Ethiopia. The pollen are triporate, and the two taxa can be distinguished from each other and from modern species using a combination of light and scanning electron microscopy, which reveals variations in the finer details of their reticulate to perforate exine sculpture. We also report a palm leaf fragment from a stratum higher in the same section that is in the Arecoideae subfamily, and most likely belongs to Sclerosperma. The implications of these discoveries for the evolutionary history of this clade of African arecoid palms is that their diversification was well underway by the middle to late Oligocene, and they were much more widespread in Africa at that time than they are now, limited to West and Central Africa. Sclerosperma exhibits ecological conservatism, as today it occurs primarily in swamps and flooded forests, and the sedimentology of the Guang River deposits at Chilga indicate a heterogeneous landscape with a high water table. The matrix containing the fossil pollen is lignite, which itself indicates standing water, and a variety of plant macrofossils from higher in the section have been interpreted as representing moist tropical forest or seasonally inundated forest communities. 相似文献
103.
Understanding the effects of anthropogenic disturbances on biodiversity is important for conservation prioritization. This study examined the effects of vegetation degradation on bird diversity in Abiata‐Shalla Lakes National Park, Ethiopia. We surveyed birds and vegetation structure between January and March 2015 in disturbed (impacted by settlement and agriculture) and undisturbed (not impacted) transects of two vegetation types (savannah woodland and gallery forest). We compared between disturbed and undisturbed transects at local (within vegetation types) and landscape (across vegetation types) levels: (a) avian species richness of the entire assemblage and feeding guilds and (b) species assemblage composition. We found significantly greater mean and total bird species richness of the entire assemblage and insectivore and granivore feeding guilds in the undisturbed transects, while the nectarivore guild was totally absent in the disturbed transects. We also found significant differences in bird species assemblage composition between the disturbed and undisturbed transects both within and across the vegetation types, and bird species assemblage composition at the landscape level was positively correlated with tree abundance and understorey vegetation height. In conclusion, our results demonstrate and add to the increasing body of evidence concerning the adverse effects of human‐induced vegetation change on bird diversity. 相似文献
104.
Hitoshi Mitsunobu Bin Zhu Seung-Joo Lee Stanley Tabor Charles C. Richardson 《The Journal of biological chemistry》2014,289(9):5860-5875
Flap endonucleases remove flap structures generated during DNA replication. Gene 6 protein of bacteriophage T7 is a 5′–3′-exonuclease specific for dsDNA. Here we show that gene 6 protein also possesses a structure-specific endonuclease activity similar to known flap endonucleases. The flap endonuclease activity is less active relative to its exonuclease activity. The major cleavage by the endonuclease activity occurs at a position one nucleotide into the duplex region adjacent to a dsDNA-ssDNA junction. The efficiency of cleavage of the flap decreases with increasing length of the 5′-overhang. A 3′-single-stranded tail arising from the same end of the duplex as the 5′-tail inhibits gene 6 protein flap endonuclease activity. The released flap is not degraded further, but the exonuclease activity then proceeds to hydrolyze the 5′-terminal strand of the duplex. T7 gene 2.5 single-stranded DNA-binding protein stimulates the exonuclease and also the endonuclease activity. This stimulation is attributed to a specific interaction between the two proteins because Escherichia coli single-stranded DNA binding protein does not produce this stimulatory effect. The ability of gene 6 protein to remove 5′-terminal overhangs as well as to remove nucleotides from the 5′-termini enables it to effectively process the 5′-termini of Okazaki fragments before they are ligated. 相似文献
105.
106.
Tran NQ Tabor S Amarasiriwardena CJ Kulczyk AW Richardson CC 《The Journal of biological chemistry》2012,287(35):29468-29478
Gene 1.7 protein is the only known nucleotide kinase encoded by bacteriophage T7. The enzyme phosphorylates dTMP and dGMP to dTDP and dGDP, respectively, in the presence of a phosphate donor. The phosphate donors are dTTP, dGTP, and ribo-GTP as well as the thymidine and guanosine triphosphate analogs ddTTP, ddGTP, and dITP. The nucleotide kinase is found in solution as a 256-kDa complex consisting of ~12 monomers of the gene 1.7 protein. The two molecular weight forms co-purify as a complex, but each form has nearly identical kinase activity. Although gene 1.7 protein does not require a metal ion for its kinase activity, the presence of Mg(2+) in the reaction mixture results in either inhibition or stimulation of the rate of kinase reactions depending on the substrates used. Both the dTMP and dGMP kinase reactions are reversible. Neither dTDP nor dGDP is a phosphate acceptor of nucleoside triphosphate donors. Gene 1.7 protein exhibits two different equilibrium patterns toward deoxyguanosine and thymidine substrates. The K(m) of 4.4 × 10(-4) m obtained with dTTP for dTMP kinase is ~3-fold higher than that obtained with dGTP for dGMP kinase (1.3 × 10(-4) m), indicating that a higher concentration of dTTP is required to saturate the enzyme. Inhibition studies indicate a competitive relationship between dGDP and both dGTP, dGMP, whereas dTDP appears to have a mixed type of inhibition of dTMP kinase. Studies suggest two functions of dTTP, as a phosphate donor and a positive effector of the dTMP kinase reaction. 相似文献
107.
Distinguishing yam species based on morphological traits is extremely difficult and unreliable, posing a challenge to breeders and genebank curators. Development of a molecular assay based on DNA barcoding can facilitate rapid and accurate identification of important Dioscorea species. To develop a DNA barcoding system forDioscorea species identification, the rbcL and matK loci (in unison and in combination), the non-coding intergenic spacer trnH-psbA of the chloroplast genome, and the nuclear ITS regions were investigated using criteria for developing candidate DNA barcodes. All DNA barcoding sequences were assessed for ease of PCR amplification, sequence quality and species discriminatory power. Amongst the markers investigated, the matK locus performed well in terms of species identification (63.2%), in addition to detecting high interspecific variation with mean divergence of 0.0196 (SD=0.0209). The combination of the two coding regions (rbcL + matK) was determined to be the optimal (76.2%) DNA barcoding approach as 16 out of 21 species could be defined. While the rbcL exhibited good PCR amplification efficiency and sequence quality, its species discriminatory power was relatively poor with 47.6% identification. Similarly, the trnH-psbA region had a weak discrimination efficiency of only 36.8%. While the development of more robust DNA barcoding systems is an ongoing challenge, our results indicate that therbcL + matK combination can be utilized as multi-locus DNA barcode regions for Dioscorea species identification. 相似文献
108.
Assimes TL Knowles JW Priest JR Basu A Volcik KA Southwick A Tabor HK Hartiala J Allayee H Grove ML Tabibiazar R Sidney S Fortmann SP Go A Hlatky M Iribarren C Boerwinkle E Myers R Risch N Quertermous T 《Human genetics》2008,123(4):399-408
Recent human genetic studies suggest that allelic variants of leukotriene pathway genes influence the risk of clinical and
subclinical atherosclerosis. We sequenced the promoter, exonic, and splice site regions of ALOX5 and ALOX5AP and then genotyped 7 SNPs in ALOX5 and 6 SNPs in ALOX5AP in 1,552 cases with clinically significant coronary artery disease (CAD) and 1,583 controls from Kaiser Permanente including
a subset of participants of the coronary artery risk development in young adults study. A nominally significant association
was detected between a promoter SNP in ALOX5 (rs12762303) and CAD in our subset of white/European subjects (adjusted odds ratio per minor allele, log-additive model,
1.32; P = 0.002). In this race/ethnic group, rs12762303 has a minor allele frequency of 15% and is tightly linked to variation at
the SP1 variable tandem repeat promoter polymorphism. However, the association between CAD and rs12762303 could not be reproduced
in the atherosclerosis risk in communities study (hazard rate ratio per minor allele; 1.08, P = 0.1). Assuming a recessive mode of inheritance, the association was not significant in either population study but our
power to detect modest effects was limited. No significant associations were observed between all other SNPs and the risk
of CAD. Overall, our findings do not support a link between common allelic variation in or near ALOX5 or ALOX5AP and the risk of CAD. However, additional studies are needed to exclude modest effects of promoter variation in ALOX5 on the risk of CAD assuming a recessive mode of inheritance.
Themistocles L. Assimes and Joshua W. Knowles contributed equally to this work. 相似文献
109.
Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describing the behavior of natural organisms and will be essential for the engineering of synthetic biological systems. Here we describe the design of synthetic constructs, termed ribosome competing RNAs (rcRNAs), as a means to rationally perturb noise in cellular gene expression. We find that noise in gene expression increases in a manner proportional to the ability of an rcRNA to compete for the cellular ribosome pool. We then demonstrate that operons significantly buffer noise between coexpressed genes in a natural cellular background and can even reduce the level of rcRNA enhanced noise. These results demonstrate that synthetic genetic constructs can significantly affect the noise profile of a living cell and, importantly, that operons are a facile genetic strategy for buffering against noise. 相似文献
110.
A photoconversion model for full spectral programming and multiplexing of optogenetic systems 下载免费PDF全文
Optogenetics combines externally applied light signals and genetically engineered photoreceptors to control cellular processes with unmatched precision. Here, we develop a mathematical model of wavelength‐ and intensity‐dependent photoconversion, signaling, and output gene expression for our two previously engineered light‐sensing Escherichia coli two‐component systems. To parameterize the model, we develop a simple set of spectral and dynamical calibration experiments using our recent open‐source “Light Plate Apparatus” device. In principle, the parameterized model should predict the gene expression response to any time‐varying signal from any mixture of light sources with known spectra. We validate this capability experimentally using a suite of challenging light sources and signals very different from those used during the parameterization process. Furthermore, we use the model to compensate for significant spectral cross‐reactivity inherent to the two sensors in order to develop a new method for programming two simultaneous and independent gene expression signals within the same cell. Our optogenetic multiplexing method will enable powerful new interrogations of how metabolic, signaling, and decision‐making pathways integrate multiple input signals. 相似文献