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91.
Frédéric D Chevalier Claudia LL Valentim Philip T LoVerde Timothy JC Anderson 《BMC genomics》2014,15(1)
Background
Identification of parasite genes that underlie traits such as drug resistance and host specificity is challenging using classical linkage mapping approaches. Extreme QTL (X-QTL) methods, originally developed by rodent malaria and yeast researchers, promise to increase the power and simplify logistics of linkage mapping in experimental crosses of schistosomes (or other helminth parasites), because many 1000s of progeny can be analysed, phenotyping is not required, and progeny pools rather than individuals are genotyped. We explored the utility of this method for mapping a drug resistance gene in the human parasitic fluke Schistosoma mansoni.Results
We staged a genetic cross between oxamniquine sensitive and resistant parasites, then between two F1 progeny, to generate multiple F2 progeny. One group of F2s infecting hamsters was treated with oxamniquine, while a second group was left untreated. We used exome capture to reduce the size of the genome (from 363 Mb to 15 Mb) and exomes from pooled F2 progeny (treated males, untreated males, treated females, untreated females) and the two parent parasites were sequenced to high read depth (mean = 95-366×) and allele frequencies at 14,489 variants compared. We observed dramatic enrichment of alleles from the resistant parent in a small region of chromosome 6 in drug-treated male and female pools (combined analysis: = 11.07, p = 8.74 × 10-29). This region contains Smp_089320 a gene encoding a sulfotransferase recently implicated in oxamniquine resistance using classical linkage mapping methods.Conclusions
These results (a) demonstrate the utility of exome capture for generating reduced representation libraries in Schistosoma mansoni, and (b) provide proof-of-principle that X-QTL methods can be successfully applied to an important human helminth. The combination of these methods will simplify linkage analysis of biomedically or biologically important traits in this parasite.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-617) contains supplementary material, which is available to authorized users. 相似文献92.
Molecular phylogeny of the major arthropod groups indicates polyphyly of crustaceans and a new hypothesis for the origin of hexapods 总被引:12,自引:6,他引:12
A phylogeny of the arthropods was inferred from analyses of amino acid
sequences derived from the nuclear genes encoding elongation factor-1 alpha
and the largest subunit of RNA polymerase II using maximum- parsimony,
neighbor-joining, and maximum-likelihood methods. Analyses of elongation
factor-1 alpha from 17 arthropods and 4 outgroup taxa recovered many
arthropod clades supported by previous morphological studies, including
Diplopoda, Myriapoda, Insecta, Hexapoda, Branchiopoda (Crustacea), Araneae,
Tetrapulmonata, Arachnida, Chelicerata, and Malacostraca (Crustacea).
However, counter to previous studies, elongation factor-1 alpha placed
Malacostraca as sister group to the other arthropods. Branchiopod
crustaceans were found to be more closely related to hexapods and myriapods
than to malacostracan crustaceans. Sequences for RNA polymerase II were
obtained from 11 arthropod taxa and were analyzed separately and in
combination with elongation factor-1 alpha. Results from these analyses
were concordant with those derived from elongation factor-1 alpha alone and
provided support for a Hexapoda/Branchiopoda clade, thus arguing against
the monophyly of the traditionally defined Atelocerata (Hexapoda +
Myriapoda).
相似文献
93.
Accessing genetic diversity for crop improvement 总被引:1,自引:0,他引:1
94.
Statistical methods of DNA sequence analysis: detection of intragenic recombination or gene conversion 总被引:28,自引:4,他引:28
Simple but exact statistical tests for detecting a cluster of associated
nucleotide changes in DNA are presented. The tests are based on the linear
distribution of a set of s sites among a total of n sites, where the s
sites may be the variable sites, sites of insertion/deletion, or
categorized in some other way. These tests are especially useful for
detecting gene conversion and intragenic recombination in a sample of DNA
sequences. In this case, the sites of interest are those that correspond to
particular ways of splitting the sequences into two groups (e.g., sequences
A and D vs. sequences B, C, and E-J). Each such split is termed a
phylogenetic partition. Application of these methods to a well-documented
case of gene conversion in human gamma-globin genes shows that sites
corresponding to two of the three observed partitions are significantly
clustered, whereas application to hominoid mitochondrial DNA
sequences--among which no recombination is expected to occur--shows no
evidence of such clustering. This indicates that clustering of
partition-specific sites is largely due to intragenic recombination or gene
conversion. Alternative hypotheses explaining the observed clustering of
sites, such as biased selection or mutation, are discussed.
相似文献
95.
H Pojski? JC Pagaduan F Babaji? E U?i?anin M Muratovi? M Tomljanovi? 《Biology of sport / Institute of Sport》2015,32(2):129-134
The aim of the present study was to compare the effects of different warm-up interventions on jump, sprint and agility performance in collegiate soccer players. Twenty-one healthy male college soccer players (age: 20.14 ± 1.65 years; body height: 179.9 ± 8.34 cm; body mass: 74.4 ± 13.0 kg; % body fat: 9.45 ± 4.8) participated in the study. Subjects underwent four different randomized warm-up protocols separated by at least 48 hours. The warm-up schemes were: 1. no conditioning contraction protocol (NCC); 2. dynamic stretching (DS); 3. prolonged intermittent low-intensity isometric exercise (ST); and, 4. ST with an additional external load equal to 30% of body weight (ST + 30% BW). All interventions were preceded by a general warm-up. Results from one-way repeated measures ANOVA demonstrated a significant difference in countermovement jump (CMJ) at F(3,60) = 10.2, ηρ2 = 0.337, p < 0.01. Post hoc analysis revealed a significant difference in CMJ performance in DS when compared to NCC and ST + 30% BW. No significant difference in CMJ was observed between DS and ST. CMJ scores in NCC, ST, and ST + 30% BW were non-significant. There was a significant difference in speed; F(3, 60) = 6.61, ηρ2 = 0.248, p < 0.01. Post hoc analysis revealed significantly better time in DS than NCC and ST. However, no difference in speed was observed between DS and ST + 30% BW. Similarly, speed was similar in NCC, ST and ST + 30% BW. A significant difference in agility performance was also observed; F(3, 60) = 24.1, ηρ2= 0.546, p < 0.01. Post hoc analysis revealed significantly greater performance gains in DS than NCC. No significant difference in agility was observed in DS, ST and ST + 30% BW. In conclusion, a prolonged intermittent low-intensity isometric protocol using bodyweight only showed similar benefits with dynamic stretching in countermovement jump performance. When the same isometric condition with additional load equal to 30% of bodyweight was applied, effects in speed and agility were similar to dynamic stretching. 相似文献
96.
Rapid screening for phenotype-genotype associations by linear transformations of genomic evaluations
Jose L Gualdrón Duarte Rodolfo JC Cantet Ronald O Bates Catherine W Ernst Nancy E Raney Juan P Steibel 《BMC bioinformatics》2014,15(1)
Background
Currently, association studies are analysed using statistical mixed models, with marker effects estimated by a linear transformation of genomic breeding values. The variances of marker effects are needed when performing the tests of association. However, approaches used to estimate the parameters rely on a prior variance or on a constant estimate of the additive variance. Alternatively, we propose a standardized test of association using the variance of each marker effect, which generally differ among each other. Random breeding values from a mixed model including fixed effects and a genomic covariance matrix are linearly transformed to estimate the marker effects.Results
The standardized test was neither conservative nor liberal with respect to type I error rate (false-positives), compared to a similar test using Predictor Error Variance, a method that was too conservative. Furthermore, genomic predictions are solved efficiently by the procedure, and the p-values are virtually identical to those calculated from tests for one marker effect at a time. Moreover, the standardized test reduces computing time and memory requirements.The following steps are used to locate genome segments displaying strong association. The marker with the highest − log(p-value) in each chromosome is selected, and the segment is expanded one Mb upstream and one Mb downstream of the marker. A genomic matrix is calculated using the information from those markers only, which is used as the variance-covariance of the segment effects in a model that also includes fixed effects and random genomic breeding values. The likelihood ratio is then calculated to test for the effect in every chromosome against a reduced model with fixed effects and genomic breeding values. In a case study with pigs, a significant segment from chromosome 6 explained 11% of total genetic variance.Conclusions
The standardized test of marker effects using their own variance helps in detecting specific genomic regions involved in the additive variance, and in reducing false positives. Moreover, genome scanning of candidate segments can be used in meta-analyses of genome-wide association studies, as it enables the detection of specific genome regions that affect an economically relevant trait when using multiple populations.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-246) contains supplementary material, which is available to authorized users. 相似文献97.
Background
Scientific workflows improve the process of scientific experiments by making computations explicit, underscoring data flow, and emphasizing the participation of humans in the process when intuition and human reasoning are required. Workflows for experiments also highlight transitions among experimental phases, allowing intermediate results to be verified and supporting the proper handling of semantic mismatches and different file formats among the various tools used in the scientific process. Thus, scientific workflows are important for the modeling and subsequent capture of bioinformatics-related data. While much research has been conducted on the implementation of scientific workflows, the initial process of actually designing and generating the workflow at the conceptual level has received little consideration. 相似文献98.
Inhaled corticosteroids (ICS) reduce COPD exacerbation frequency and slow decline in health related quality of life but have little effect on lung function, do not reduce mortality, and increase the risk of pneumonia. We systematically reviewed trials in which ICS have been withdrawn from patients with COPD, with the aim of determining the effect of withdrawal, understanding the differing results between trials, and making recommendations for improving methodology in future trials where medication is withdrawn. Trials were identified by two independent reviewers using MEDLINE, EMBASE and CINAHL, citations of identified studies were checked, and experts contacted to identify further studies. Data extraction was completed independently by two reviewers. The methodological quality of each trial was determined by assessing possible sources of systematic bias as recommended by the Cochrane collaboration. We included four trials; the quality of three was adequate. In all trials, outcomes were generally worse for patients who had had ICS withdrawn, but differences between outcomes for these patients and patients who continued with medication were mostly small and not statistically significant. Due to data paucity we performed only one meta-analysis; this indicated that patients who had had medication withdrawn were 1.11 (95% CI 0.84 to 1.46) times more likely to have an exacerbation in the following year, but the definition of exacerbations was not consistent between the three trials, and the impact of withdrawal was smaller in recent trials which were also trials conducted under conditions that reflected routine practice. There is no evidence from this review that withdrawing ICS in routine practice results in important deterioration in patient outcomes. Furthermore, the extent of increase in exacerbations depends on the way exacerbations are defined and managed and may depend on the use of other medication. In trials where medication is withdrawn, investigators should report other medication use, definitions of exacerbations and management of patients clearly. Intention to treat analyses should be used and interpreted appropriately. 相似文献
99.
Biophysical Reviews - Molecular motors are enzymes that convert chemical potential energy into controlled kinetic energy for mechanical work inside cells. Understanding the biophysics of these... 相似文献
100.