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101.
Multi-category classification methods were used to detect SNP-mortality associations in broilers. The objective was to select a subset of whole genome SNPs associated with chick mortality. This was done by categorizing mortality rates and using a filter-wrapper feature selection procedure in each of the classification methods evaluated. Different numbers of categories (2, 3, 4, 5 and 10) and three classification algorithms (naïve Bayes classifiers, Bayesian networks and neural networks) were compared, using early and late chick mortality rates in low and high hygiene environments. Evaluation of SNPs selected by each classification method was done by predicted residual sum of squares and a significance test-related metric. A naïve Bayes classifier, coupled with discretization into two or three categories generated the SNP subset with greatest predictive ability. Further, an alternative categorization scheme, which used only two extreme portions of the empirical distribution of mortality rates, was considered. This scheme selected SNPs with greater predictive ability than those chosen by the methods described previously. Use of extreme samples seems to enhance the ability of feature selection procedures to select influential SNPs in genetic association studies. 相似文献
102.
Davidson WS Koop BF Jones SJ Iturra P Vidal R Maass A Jonassen I Lien S Omholt SW 《Genome biology》2010,11(9):403
The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies
and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids. 相似文献
103.
Steven JM Jones Janessa Laskin Yvonne Y Li Obi L Griffith Jianghong An Mikhail Bilenky Yaron S Butterfield Timothee Cezard Eric Chuah Richard Corbett Anthony P Fejes Malachi Griffith John Yee Montgomery Martin Michael Mayo Nataliya Melnyk Ryan D Morin Trevor J Pugh Tesa Severson Sohrab P Shah Margaret Sutcliffe Angela Tam Jefferson Terry Nina Thiessen Thomas Thomson Richard Varhol Thomas Zeng Yongjun Zhao Richard A Moore David G Huntsman Inanc Birol Martin Hirst Robert A Holt Marco A Marra 《Genome biology》2010,11(8):1-12
Background
Adenocarcinomas of the tongue are rare and represent the minority (20 to 25%) of salivary gland tumors affecting the tongue. We investigated the utility of massively parallel sequencing to characterize an adenocarcinoma of the tongue, before and after treatment.Results
In the pre-treatment tumor we identified 7,629 genes within regions of copy number gain. There were 1,078 genes that exhibited increased expression relative to the blood and unrelated tumors and four genes contained somatic protein-coding mutations. Our analysis suggested the tumor cells were driven by the RET oncogene. Genes whose protein products are targeted by the RET inhibitors sunitinib and sorafenib correlated with being amplified and or highly expressed. Consistent with our observations, administration of sunitinib was associated with stable disease lasting 4 months, after which the lung lesions began to grow. Administration of sorafenib and sulindac provided disease stabilization for an additional 3 months after which the cancer progressed and new lesions appeared. A recurring metastasis possessed 7,288 genes within copy number amplicons, 385 genes exhibiting increased expression relative to other tumors and 9 new somatic protein coding mutations. The observed mutations and amplifications were consistent with therapeutic resistance arising through activation of the MAPK and AKT pathways.Conclusions
We conclude that complete genomic characterization of a rare tumor has the potential to aid in clinical decision making and identifying therapeutic approaches where no established treatment protocols exist. These results also provide direct in vivo genomic evidence for mutational evolution within a tumor under drug selection and potential mechanisms of drug resistance accrual. 相似文献104.
The evolutionary analysis of the Tnt1 retrotransposon in Nicotiana species reveals the high variability of its regulatory sequences 总被引:2,自引:0,他引:2
We studied the evolution of the tobacco Tnt1 retrotransposon by analyzing
Tnt1 partial sequences containing both coding domains and U3 regulatory
sequences obtained from a number of Nicotiana species. We detected three
different subfamilies of Tnt1 elements, Tnt1A, Tnt1B, and Tnt1C, that
differ completely in their U3 regions but share conserved flanking coding
and LTR regions. U3 divergence between the three subfamilies is found in
the region that contains the regulatory sequences that control the
expression of the well-characterized Tnt1-94 element. This suggests that
expression of the three Tnt1 subfamilies might be differently regulated.
The three Tnt1 subfamilies were present in the Nicotiana genome at the time
of species divergence, but have evolved independently since then in the
different genomes. Each Tnt1 subfamily seems to have conserved its ability
to transpose in a limited and different number of Nicotiana species. Our
results illustrate the high variability of Tnt1 regulatory sequences. We
propose that this high sequence variability could allow these elements to
evolve regulatory mechanisms in order to optimize their coexistence with
their host genome.
相似文献
105.
106.
Cross-adaptation and molecular modeling study of receptor mechanisms common to four taste stimuli in humans 总被引:2,自引:2,他引:0
Psychophysical cross-adaptation experiments were performed with two
carbohydrates, sucrose (SUC) and fructose (FRU), and two sweeteners,
acesulfame-K (MOD) and dulcin (DUL). Seven subjects were asked to match
concentrations that elicited the same intensity as a sucrose reference (30
g/l). Cross-adaptation levels were calculated as the ratio of isointense
concentrations measured for a given stimulus before and under adaptation.
On average, cross-adaptation between SUC and FRU is low and apparently
reciprocal. By contrast, cross-adaptation between SUC and MOD is clearly
non-reciprocal: SUC adapts MOD significantly (24%, P < 0.005), but MOD
fails to adapt SUC (2%, P < 0.79). Significant and reciprocal
cross-enhancement is observed between DUL and MOD (approximately -20%, P
< 0.03), and also between SUC and DUL (approximately -15%, P < 0.08).
In parallel, molecular modeling of the four tastants was performed in order
to look for the 12 common binding motifs that were isolated on 14 other
tastants in a previous study. SUC and FRU each display 10 out of the 12
binding motifs, whereas DUL and MOD only display four and five distinct
motifs respectively and do not have any motif in common. Experimental
cross-adaptation levels seem to correlate well with the number of motifs
that molecules have in common. FRU and SUC share a majority of binding
motifs and correlatively show mutual cross-adaptation. Four motifs of MOD
are found among the 10 motifs of SUC, which may explain why SUC
cross-adapts MOD but not vice versa. By contrast, DUL and MOD do not share
any motif and do not cross- adapt. The various molecular mechanisms that
may be responsible for cross-adaptation and/or cross-enhancement are
discussed in light of our results.
相似文献
107.
Liu H Cunnick JE Hendrich S 《Prostaglandins, leukotrienes, and essential fatty acids》2000,63(3):153-158
Strain differences in cancer incidence are proposed to be due partly to differences in immune function. As potential cancer-associated immunological regulators, the concentrations of hepatic prostaglandins E(2)(PGE(2 alpha)and F(2 alpha)(PGF(2 alpha)) were compared in 9-week-old male and female F344/N and Sprague-Dawley (SD) rats. There were no strain or gender differences in the concentrations of hepatic PGE(2). No strain difference was found in the concentration of hepatic PGF(2 alpha), but the hepatic PGF(2 alpha)concentration in female rats was two-fold that of the male rat (130 vs 60 ng/g). PGE(2)significantly inhibited hepatic natural-killer cell (NK) activity in vitro compared with untreated cells from both genders and strains (P<0.05), 25 ng PGE(2)/ml inhibited NK activity significantly more than did 10 ng PGE(2)/ml (P<0.05). In contrast, 50 ng PGF(2 alpha)/ml and 100 ng PGF(2 alpha)/ml significantly stimulated hepatic NK activity compared with untreated hepatic cells from both F344/N and SD rats. This study suggests that prostaglandins may have a negligible net effect on NK activity associated with rat liver, and may be unlikely to mediate cancer-related immune function. 相似文献
108.
Background
A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy.Results
The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors.The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity.Conclusion
Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence.109.
Efficient estimation of the prevalence of multiple rare traits 总被引:1,自引:0,他引:1
110.
Youngjin Cho Rachel Silverstein Max T. Geisinger Stephen Martinkovich Holly Corkill Jess M. Cunnick Sonia L. Planey John A. Arnott 《PloS one》2015,10(9)