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131.
Adam H. Freedman Rena M. Schweizer Diego Ortega-Del Vecchyo Eunjung Han Brian W. Davis Ilan Gronau Pedro M. Silva Marco Galaverni Zhenxin Fan Peter Marx Belen Lorente-Galdos Oscar Ramirez Farhad Hormozdiari Can Alkan Carles Vilà Kevin Squire Eli Geffen Josip Kusak Adam R. Boyko Heidi G. Parker Clarence Lee Vasisht Tadigotla Adam Siepel Carlos D. Bustamante Timothy T. Harkins Stanley F. Nelson Tomas Marques-Bonet Elaine A. Ostrander Robert K. Wayne John Novembre 《PLoS genetics》2016,12(3)
Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. 相似文献
132.
Exploring the influence of shrubs on herbaceous communities in a Mediterranean climatic context of two spatial scales 总被引:1,自引:0,他引:1
Jaime Madrigal Jose Antonio García-Rodriguez Roberto Julian Angel Puerto Belen Fernández-Santos 《Plant Ecology》2008,199(2):225-234
Communities of plants determine nonrandom spatial patterns defined by the intervention of abiotic and biotic factors acting
at different spatial scales. We consider the influence of shrubs as one of the most important factors (biotic) affecting these
spatial patterns at microscale. The macroclimate could be considered one of the most important factors (abiotic) at regional
scale. To study the role and the floristic implications of each factor on the global patterns of herbaceous communities, we
have developed a stratified sampling design that integrates both micro and macroscale on a 100 Km-long transect (east–west)
in western central Spain. The results suggest that macroclimate could be one of the most important factors in determining
herbaceous spatial patterns. Moreover, shrubs create a microspatial environmental heterogeneity that could alter such global
climate patterns, modifying the spatial affinities established among species. This implies that environmental heterogeneity
related to microhabitat could play a key role in spatial patterns at broad spatial scales, and consequently in the dynamics
of the distribution and establishment of herbaceous species. 相似文献
133.
M. Guadalupe Martinez M. Belen Forlenza Nélida A. Candurra Dr. 《Biotechnology journal》2009,4(6):866-870
Junin arenavirus (JUNV) entry is dependent on clathrin-mediated pathways and it relies on the integrity of the actin cytoskeleton as well as the dynamics of microtubules. To determine the method of entry used by this human pathogen, we have demonstrated that in Vero cells JUNV is trafficked via the cellular dynamin 2 (dyn2) endocytic pathway and it is dependent on the Eps15 GTPase. In addition, we have shown that the virus travels through Rab5-mediated early and Rab7-mediated late endosomes in its pH-dependent entry. Altogether, this study gives further inside into the endocytic pathway utilized by the arenavirus JUNV 相似文献
134.
Noemí Eiró Lucía González Luis O. González Belen Fernandez-Garcia Maria Luz Lamelas Laura Marín Salomé González-Reyes José Manuel del Casar Francisco J. Vizoso 《PloS one》2012,7(11)
Inflammatory conditions may promote tumor progression and aggressiveness. In previous reports, we found a group of breast cancer tumors characterized by metalloprotease-11 (MMP-11) expression by intratumoral mononuclear inflammatory cells (MICs), which was associated with distant metastasis development. Thus, in the present study we evaluated the relationship between MMP-11 expression by MICs, distant metastasis development, and a wide panel of inflammatory factors in breast carcinoma. In an initial approach, we analyzed 65 factors associated with tumor progression and inflammation, in a tumor population classified in good or bad prognosis, based on MMP-11 expression by intratumoral MICs. The most differentially expressed factors were then analyzed in a wider tumor population classified according to MMP-11 expression by MICs and also according to metastasis development. These analyses were carried out by Real-time PCR. The results showed that of the 65 starting factors analyzed, those related with MMP-11 expression by MICs were: IL-1, −5, −6, −8, −17, −18, MMP-1, TIMP-1, ADAM-8, −10, −15, −23, ADAMTS-1, −2, −15, Annexin A2, IFNβ, Claudin-3, CCL-3, MyD88, IRAK-4 and NFκB. Of them, factors more differentially expressed between both groups of tumors were IL-1, IL-5, IL-6, IL-17, IFNβ and NFκB. Thereafter, we confirmed in the wider tumor population, that there is a higher expression of those factors in tumors infiltrated by MMP-11 positive MICs. Altogether these results indicate that tumors developing worse prognosis and identified by MMP-11 expression by intratumoral MICs, shows an up-regulation of inflammatory-related genes. 相似文献
135.
All��via Rouse Ferreira dos Santos Ana M. Ramos-Cabrer M Belen D��az-Hern��ndez Santiago Pereira-Lorenzo 《Tree Genetics & Genomes》2011,7(5):1041-1056
This is the first known large-scale molecular study of simple sequence repeats loci based on pear cultivars from the northwestern
Iberian Peninsula. Most of the Spanish pear crop (one of the largest in Europe) is based on the Spanish cultivar Blanquilla
and various other foreign cultivars. However, local cultivars can still be found in old orchards in northwestern Spain. Between
1978 and 1981, the Centro de Investigaciones Agrarias de Mabegondo (Xunta de Galicia) established a Germplasm Bank of local
pear cultivars containing 221 accessions. In the current study, these were analysed and compared with 20 commercial cultivars
of Pyrus spp. using 19 microsatellites. We identified 127 genotypes out of 221 accessions with an average of 43% clonality in this
collection. Genotypes were analysed using a model-based Bayesian procedure (Structure), factorial correspondence analysis
and molecular variance analysis, and Jaccard coefficients were estimated. Four reconstructed populations were identified by
Structure, one related to Asian cultivars, two to French and English cultivars and one to Galician cultivars. The four identified
groups of pears had evolved independently. This study explains the diversification process in pear cultivars from northwestern
cultivars based on hybridization (16%), selection of triploids (38%) and the introgression of commercial cultivars in the
collection (4%). 相似文献
136.
María Isabel Queipo-Ortu?o Xavier Escoté Victoria Ceperuelo-Mallafré Lourdes Garrido-Sanchez Merce Miranda Mercedes Clemente-Postigo Rafael Pérez-Pérez Belen Peral Fernando Cardona Jose Manuel Fernández-Real Francisco J. Tinahones Joan Vendrell 《PloS one》2012,7(11)
Background
FABP4 is predominantly expressed in adipose tissue, and its circulating levels are linked with obesity and a poor atherogenic profile.Objective
In patients with a wide BMI range, we analyze FABP4 expression in adipose and hepatic tissues in the settings of obesity and insulin resistance. Associations between FABP4 expression in adipose tissue and the FABP4 plasma level as well as the main adipogenic and lipolytic genes expressed in adipose tissue were also analyzed.Methods
The expression of several lipogenic, lipolytic, PPAR family and FABP family genes was analyzed by real time PCR. FABP4 protein expression in total adipose tissues and its fractions were determined by western blot.Results
In obesity FABP4 expression was down-regulated (at both mRNA and protein levels), with its levels mainly predicted by ATGL and inversely by the HOMA-IR index. The BMI appeared as the only determinant of the FABP4 variation in both adipose tissue depots. FABP4 plasma levels showed a significant progressive increase according to BMI but no association was detected between FABP4 circulating levels and SAT or VAT FABP4 gene expression. The gene expression of FABP1, FABP4 and FABP5 in hepatic tissue was significantly higher in tissue from the obese IR patients compared to the non-IR group.Conclusion
The inverse pattern in FABP4 expression between adipose and hepatic tissue observed in morbid obese patients, regarding the IR context, suggests that both tissues may act in a balanced manner. These differences may help us to understand the discrepancies between circulating plasma levels and adipose tissue expression in obesity. 相似文献137.
Mariana Raineri Betina Gonzalez Belen Goitia Edgar Garcia-Rill Irina N. Krasnova Jean Lud Cadet Francisco J. Urbano Veronica Bisagno 《PloS one》2012,7(10)
Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4×5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2×90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum. 相似文献
138.
Göksel H Wasserberg D Möcklinghoff S Araujo BV Brunsveld L 《Bioorganic & medicinal chemistry》2011,19(1):306-311
An efficient and rapid on-bead screening method was established to identify non-natural peptides that target the Androgen Receptor-cofactor interaction. Binding of the Androgen Receptor ligand binding domain to peptide sequences displayed on beads in a One-Bead-One-Compound format could be screened using fluorescence microscopy. The method was applied to generate and screen both a focussed and a random peptide library. Resynthesis of the peptide hits allowed for the verification of the affinity of the selected peptides for the Androgen Receptor in a competitive fluorescence polarization assay. For both libraries strong Androgen Receptor binding peptides were found, both with non-natural and natural amino acids. The peptides identified with natural amino acids showed great similarity in terms of preferred amino acid sequence with peptides previously isolated from biological screens, thus validating the screening approach. The non-natural peptides featured important novel chemical transformations on the relevant hydrophobic amino acid positions interacting with the Androgen Receptor. This screening approach expands the molecular diversity of peptide inhibitors for nuclear receptors. 相似文献
139.
Carrancio S Blanco B Romo C Muntion S Lopez-Holgado N Blanco JF Briñon JG San Miguel JF Sanchez-Guijo FM del Cañizo MC 《PloS one》2011,6(10):e26241
The aim of the present study was to determine how mesenchymal stem cells (MSC) could improve bone marrow (BM) stroma function after damage, both in vitro and in vivo. Human MSC from 20 healthy donors were isolated and expanded. Mobilized selected CD34(+) progenitor cells were obtained from 20 HSCT donors. For in vitro study, long-term bone marrow cultures (LTBMC) were performed using a etoposide damaged stromal model to test MSC effect in stromal confluence, capability of MSC to lodge in stromal layer as well as some molecules (SDF1, osteopontin,) involved in hematopoietic niche maintenance were analyzed. For the in vivo model, 64 NOD/SCID recipients were transplanted with CD34+ cells administered either by intravenous (i.v.) or intrabone (i.b.) route, with or without BM derived MSC. MSC lodgement within the BM niche was assessed by FISH analysis and the expression of SDF1 and osteopontin by immunohistochemistry. In vivo study showed that when the stromal damage was severe, TP-MSC could lodge in the etoposide-treated BM stroma, as shown by FISH analysis. Osteopontin and SDF1 were differently expressed in damaged stroma and their expression restored after TP-MSC addition. Human in vivo MSC lodgement was observed within BM niche by FISH, but MSC only were detected and not in the contralateral femurs. Human MSC were located around blood vessels in the subendoestal region of femurs and expressed SDF1 and osteopontin. In summary, our data show that MSC can restore BM stromal function and also engraft when a higher stromal damage was done. Interestingly, MSC were detected locally where they were administered but not in the contralateral femur. 相似文献
140.
Belén Lloveras Silvia Gomez Francesc Alameda Beatriz Bellosillo Sergi Mojal Mercè Muset Manuel Parra José Carlos Palomares Sergi Serrano 《PloS one》2013,8(3)