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Detecting non-neutral heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence 总被引:11,自引:4,他引:7
Natural selection, in the form of balancing selection or selective sweeps,
can result in a decoupling of the amounts of molecular polymorphism and
divergence. Thus natural selection can cause some areas of DNA sequence to
have greater silent polymorphism, relative to divergence between species,
than other areas. It would be useful to have a statistical test for
heterogeneity in the polymorphism to divergence ratio across a region of
DNA sequence, one that could identify heterogeneity greater than that
expected from the neutral processes of mutation, drift, and recombination.
The only currently available test requires that a region be arbitrarily
divided into sections that are compared with each other, and the
subjectivity of this division could be problematic. Here a test is proposed
in which runs of polymorphic and fixed sites are counted, where a "run" is
a set of one or more sites of one type preceded and followed by the other
type. The number of runs is smaller than otherwise expected if
polymorphisms are clumped together. By simulating neutral evolution and
comparing the observed number of runs to the simulations, a statistical
test is possible which does not require any a priori decisions about
subdivision.
相似文献
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Janine JH Oosterhof G Jolanda Elving Ietse Stokroos Arie van nieuw Amerongen Henny C van der Mei Henk J Busscher 《Biofouling》2013,29(6):347-353
The integrity of biofilms on voice prostheses used to rehabilitate speech in laryngectomized patients causes unwanted increases in airflow resistance, impeding speech. Biofilm integrity is ensured by extracellular polymeric substances (EPS). This study aimed to determine whether synthetic salivary peptides or mucolytics, including N-acetylcysteine and ascorbic acid, influence the integrity of voice prosthetic biofilms. Biofilms were grown on voice prostheses in an artificial throat model and exposed to synthetic salivary peptides, mucolytics and two different antiseptics (chlorhexidine and Triclosan). Synthetic salivary peptides did not reduce the air flow resistance of voice prostheses after biofilm formation. Although both chlorhexidine and Triclosan reduced microbial numbers on the prostheses, only the Triclosan-containing positive control reduced the air flow resistance. Unlike ascorbic acid, the mucolytic N-acetylcysteine removed most EPS from the biofilms and induced a decrease in air flow resistance. 相似文献
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Improved tests for heterogeneity across a region of DNA sequence in the ratio of polymorphism to divergence 总被引:15,自引:9,他引:6
The neutral theory of molecular evolution predicts that the ratio of
polymorphisms to fixed differences should be fairly uniform across a region
of DNA sequence. Significant heterogeneity in this ratio can indicate the
effects of balancing selection, selective sweeps, mildly deleterious
mutations, or background selection. Comparing an observed heterogeneity
statistic with simulations of the heterogeneity resulting from random
phylogenetic and sampling variation provides a test of the statistical
significance of the observed pattern. When simulated data sets containing
heterogeneity in the polymorphism-to-divergence ratio are examined,
different statistics are most powerful for detecting different patterns of
heterogeneity. The number of runs is most powerful for detecting patterns
containing several peaks of polymorphism; the Kolmogorov-Smirnov statistic
is most powerful for detecting patterns in which one end of the gene has
high polymorphism and the other end has low polymorphism; and a newly
developed statistic, the mean sliding G statistic, is most powerful for
detecting patterns containing one or two peaks of polymorphism with reduced
polymorphism on either side. Nine out of 27 genes from the Drosophila
melanogaster subgroup exhibit heterogeneity that is significant under at
least one of these three tests, with five of the nine remaining significant
after a correction for multiple comparisons, suggesting that detectable
evidence for the effects of some kind of selection is fairly common.
相似文献
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Jožica Dolenc John H. Missimer Michel O. Steinmetz Wilfred F. van Gunsteren 《Journal of biomolecular NMR》2010,47(3):221-235
The C-terminal trigger sequence is essential in the coiled-coil formation of GCN4-p1; its conformational properties are thus
of importance for understanding this process at the atomic level. A solution NMR model structure of a peptide, GCN4p16–31,
encompassing the GCN4-p1 trigger sequence was proposed a few years ago. Derived using a standard single-structure refinement
protocol based on 172 nuclear Overhauser effect (NOE) distance restraints, 14 hydrogen-bond and 11 ϕ torsional-angle restraints,
the resulting set of 20 NMR model structures exhibits regular α-helical structure. However, the set slightly violates some
measured NOE bounds and does not reproduce all 15 measured 3J(HN-HCα)-coupling constants, indicating that different conformers of GCN4p16–31 might be present in solution. With the aim to resolve
structures compatible with all NOE upper distance bounds and 3J-coupling constants, we executed several structure refinement protocols employing unrestrained and restrained molecular dynamics
(MD) simulations with two force fields. We find that only configurational ensembles obtained by applying simultaneously time-averaged
NOE distance and 3J-coupling constant restraining with either force field reproduce all the experimental data. Additionally, analyses of the
simulated ensembles show that the conformational variability of GCN4p16–31 in solution admitted by the available set of 187
measured NMR data is larger than represented by the set of the NMR model structures. The conformations of GCN4p16–31 in solution
differ in the orientation not only of the side-chains but also of the backbone. The inconsistencies between the NMR model
structures and the measured NMR data are due to the neglect of averaging effects and the inclusion of hydrogen-bond and torsional-angle
restraints that have little basis in the primary, i.e. measured NMR data. 相似文献
10.
David?E?Comings Thomas?JH?Chen Kenneth?BlumEmail author Julie?F?Mengucci Seth?H?Blum Brian?Meshkin 《Theoretical biology & medical modelling》2005,2(1):50