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21.
Cloned transchromosomic calves producing human immunoglobulin 总被引:16,自引:0,他引:16
22.
The Framingham Heart Study offspring cohort, a complex data set with irregularly spaced longitudinal phenotype data, was made available as part of Genetic Analysis Workshop 13. To allow an analysis of all of the data simultaneously, a mixed-model- based random-regression (RR) approach was used. The RR accounted for the variation in genetic effects (including marker-specific quantitative trait locus (QTL) effects) across time by fitting polynomials of age. The use of a mixed model allowed both fixed (such as sex) and random (such as familial environment) effects to be accounted for appropriately. Using this method we performed a QTL analysis of all of the available adult phenotype data (26,106 phenotypic records). In addition to RR, conventional univariate variance component techniques were applied. The traits of interest were BMI, HDLC, total cholesterol, and height. The longitudinal method allowed the characterization of the change in QTL effects with aging. A QTL affecting BMI was shown to act mainly at early ages. 相似文献
23.
Multitrait least squares for quantitative trait loci detection 总被引:20,自引:0,他引:20
A multiple-trait QTL mapping method using least squares is described. It is presented as an extension of a single-trait method for use with three-generation, outbred pedigrees. The multiple-trait framework allows formal testing of whether the same QTL affects more than one trait (i.e., a pleiotropic QTL) or whether more than one linked QTL are segregating. Several approaches to the testing procedure are presented and their suitability discussed. The performance of the method is investigated by simulation. As previously found, multitrait analyses increase the power to detect a pleiotropic QTL and the precision of its location estimate. With enough information, discrimination between alternative genetic models is possible. 相似文献
24.
Gorelick RJ Lifson JD Yovandich JL Rossio JL Piatak M Scarzello AJ Knott WB Bess JW Fisher BA Flynn BM Henderson LE Arthur LO Benveniste RE 《Journal of medical primatology》2000,29(3-4):209-219
A simian immunodeficiency virus (SIV)(Mne) DNA clone was constructed that produces viruses containing a four amino acid deletion in the second zinc finger of the nucleocapsid (NC) domain of the Gag polyprotein. Viruses produced from this clone, although non-infectious both in vitro and in vivo, complete a majority of the steps in a single retroviral infection cycle. Eight pig-tailed macaques (Macaca nemestrina) were inoculated intramuscularly and subcutaneously three times over the course of 24 weeks with the NC mutant expressing DNA. These macaques, and four controls, were then challenged mucosally (intrarectally) with the homologous virus (SIV Mne CL E11S) and monitored for evidence of infection and clinical disease. Prior to challenge, a measurable humoral immune response was noted in four of eight immunized macaques. After challenge, all 12 macaques became infected, although four immunized animals greatly restricted their viral replication, and one immunized animal that controlled replication remains antibody negative. No disease has been evidence during the 46-week period of monitoring after challenge. 相似文献
25.
Phylogenetic relationships were determined for 76 partial P-element
sequences from 14 species of the melanogaster species group within the
Drosophila subgenus Sophophora. These results are examined in the context
of the phylogeny of the species from which the sequences were isolated.
Sequences from the P-element family fall into distinct subfamilies, or
clades, which are often characteristic for particular species subgroups.
When examined locally among closely related species, the evolution of P
elements is characterized by vertical transmission, whereby the P-element
phylogeny traces the species phylogeny. On a broader scale, however, the
P-element phylogeny is not congruent with the species phylogeny. One
feature of P-element evolution in the melanogaster group is the presence of
more than one P-element subfamily, differing by as much as 36%, in the
genomes of some species. Thus, P elements from several individual species
are not monophyletic, and a likely explanation for the incongruence between
P-element and species phylogenies is provided by the comparison of
paralogous sequences. In certain instances, horizontal transfer seems to be
a valid alternative explanation for lack of congruence between species and
P-element phylogenies. The canonical P-element subfamily, which represents
the active, autonomous transposable element, is restricted to D.
melanogaster. Thus, its origin clearly lies outside of the melanogaster
species group, consistent with the earlier conclusion of recent horizontal
transfer.
相似文献
26.
COMT polymorphism modulates the resting‐state EEG alpha oscillatory response to acute nicotine in male non‐smokers
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H. Bowers D. Smith S. de la Salle J. Choueiry D. Impey T. Philippe H. Dort A. Millar M. Daigle P. R. Albert A. Beaudoin V. Knott 《Genes, Brain & Behavior》2015,14(6):466-476
Performance improvements in cognitive tasks requiring executive functions are evident with nicotinic acetylcholine receptor (nAChR) agonists, and activation of the underlying neural circuitry supporting these cognitive effects is thought to involve dopamine neurotransmission. As individual difference in response to nicotine may be related to a functional polymorphism in the gene encoding catechol‐O‐methyltransferase (COMT), an enzyme that strongly influences cortical dopamine metabolism, this study examined the modulatory effects of the COMT Val158Met polymorphism on the neural response to acute nicotine as measured with resting‐state electroencephalographic (EEG) oscillations. In a sample of 62 healthy non‐smoking adult males, a single dose (6 mg) of nicotine gum administered in a randomized, double‐blind, placebo‐controlled design was shown to affect α oscillatory activity, increasing power of upper α oscillations in frontocentral regions of Met/Met homozygotes and in parietal/occipital regions of Val/Met heterozygotes. Peak α frequency was also found to be faster with nicotine (vs. placebo) treatment in Val/Met heterozygotes, who exhibited a slower α frequency compared to Val/Val homozygotes. The data tentatively suggest that interindividual differences in brain α oscillations and their response to nicotinic agonist treatment are influenced by genetic mechanisms involving COMT. 相似文献
27.
Agata Rekas Robert B. Knott Anna Sokolova Kevin J. Barnham Keyla A. Perez Colin L. Masters Simon C. Drew Roberto Cappai Cyril C. Curtain Chi L. L. Pham 《European biophysics journal : EBJ》2010,39(10):1407-1419
Inclusions of aggregated α-synuclein (α-syn) in dopaminergic neurons are a characteristic histological marker of Parkinson’s
disease (PD). In vitro, α-syn in the presence of dopamine (DA) at physiological pH forms SDS-resistant non-amyloidogenic oligomers.
We used a combination of biophysical techniques, including sedimentation velocity analysis, small angle X-ray scattering (SAXS)
and circular dichroism spectroscopy to study the characteristics of α-syn oligomers formed in the presence of DA. Our SAXS
data show that the trimers formed by the action of DA on α-syn consist of overlapping worm-like monomers, with no end-to-end
associations. This lack of structure contrasts with the well-established, extensive β-sheet structure of the amyloid fibril
form of the protein and its pre-fibrillar oligomers. We propose on the basis of these and earlier data that oxidation of the
four methionine residues at the C- and N-terminal ends of α-syn molecules prevents their end-to-end association and stabilises
oligomers formed by cross linking with DA-quinone/DA-melanin, which are formed as a result of the redox process, thus inhibiting
formation of the β-sheet structure found in other pre-fibrillar forms of α-syn. 相似文献
28.
Robert G. Doupé Jim Mitchell Matthew J. Knott Aaron M. Davis Alan J. Lymbery 《Wetlands Ecology and Management》2010,18(1):69-78
Foraging by feral pigs can strongly affect wetland vegetation assemblages and so too wider ecological processes, although
their effects on freshwater ecosystems have seldom been studied. We assessed the ecological effects of pig foraging in replicate
fenced and unfenced ephemeral floodplain lagoons in tropical north-eastern Australia. Pig foraging activities in unfenced
lagoons caused major changes to aquatic macrophyte communities and as a consequence, to the proportional amounts of open water
and bare ground. The destruction of macrophyte communities and upheaval of wetland sediments significantly affected wetland
turbidity, and caused prolonged anoxia and pH imbalances in the unfenced treatments. Whilst fencing of floodplain lagoons
will protect against feral pig foraging activities, our repeated measures of many biological, physical and chemical parameters
inferred that natural seasonal (i.e. temporal) effects had a greater influence on these variables than did pigs. To validate
this observation requires measuring how these effects are influenced by the seemingly greater annual disturbance regime of
variable flooding and drying in this tropical climate. 相似文献
29.
30.
Jose MG Vilar 《BMC systems biology》2010,4(1):152