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991.
Takehiko Shimizu Bao Ho Kathleen Deeley Jessica Brise?o-Ruiz Italo M. Faraco Jr Brett I. Schupack Jo?o A. Brancher Giovana D. Pecharki Erika C. Küchler Patricia N. Tannure Andrea Lips Thays C. S. Vieira Asli Patir Mine Yildirim Fernando A. Poletta Juan C. Mereb Judith M. Resick Carla A. Brandon Iêda M. Orioli Eduardo E. Castilla Mary L. Marazita Figen Seymen Marcelo C. Costa José M. Granjeiro Paula C. Trevilatto Alexandre R. Vieira 《PloS one》2012,7(9)
There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes may contribute to caries. For the present study, we used DNA samples collected from 1,831 individuals from various population data sets. Single nucleotide polymorphism markers were genotyped in selected genes (ameloblastin, amelogenin, enamelin, tuftelin, and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Associations with caries experience can be detected but they are not necessarily replicated in all population groups and the most expressive results was for a marker in AMELX (p = 0.0007). To help interpret these results, we evaluated if enamel microhardness changes under simulated cariogenic challenges are associated with genetic variations in these same genes. After creating an artificial caries lesion, associations could be seen between genetic variation in TUFT1 (p = 0.006) and TUIP11 (p = 0.0006) with enamel microhardness. Our results suggest that the influence of genetic variation of enamel formation genes may influence the dynamic interactions between the enamel surface and the oral cavity. 相似文献
992.
Thrombospondin-1 interacts with Trypanosoma cruzi surface calreticulin to enhance cellular infection
CA Johnson YY Kleshchenko AO Ikejiani AN Udoko TC Cardenas S Pratap MA Duquette MF Lima J Lawler F Villalta PN Nde 《PloS one》2012,7(7):e40614
Trypanosoma cruzi causes Chagas disease, which is a neglected tropical disease that produces severe pathology and mortality. The mechanisms by which the parasite invades cells are not well elucidated. We recently reported that T. cruzi up-regulates the expression of thrombospondin-1 (TSP-1) to enhance the process of cellular invasion. Here we characterize a novel TSP-1 interaction with T. cruzi that enhances cellular infection. We show that labeled TSP-1 interacts specifically with the surface of T. cruzi trypomastigotes. We used TSP-1 to pull down interacting parasite surface proteins that were identified by mass spectrometry. We also show that full length TSP-1 and the N-terminal domain of TSP-1 (NTSP) interact with T. cruzi surface calreticulin (TcCRT) and other surface proteins. Pre-exposure of recombinant NTSP or TSP-1 to T. cruzi significantly enhances cellular infection of wild type mouse embryo fibroblasts (MEF) compared to the C-terminal domain of TSP-1, E3T3C1. In addition, blocking TcCRT with antibodies significantly inhibits the enhancement of cellular infection mediated by the TcCRT-TSP-1 interaction. Taken together, our findings indicate that TSP-1 interacts with TcCRT on the surface of T. cruzi through the NTSP domain and that this interaction enhances cellular infection. Thus surface TcCRT is a virulent factor that enhances the pathogenesis of T. cruzi infection through TSP-1, which is up-regulated by the parasite. 相似文献
993.
Atila Iamarino Fernando Lucas de Melo Carla Torres Braconi Paolo Marinho de Andrade Zanotto 《PloS one》2012,7(4)
Although some studies have shown diversity in HIV integrase (IN) genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes), 17 of subtype F (8 of which were found in recombinant genomes), 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2) that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL) or elvitegravir (EVG) resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS) indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population. 相似文献
994.
Prediction accuracies of estimated breeding values for economically important traits are expected to benefit from genomic information. Single nucleotide polymorphism (SNP) panels used in genomic prediction are increasing in density, but the Markov Chain Monte Carlo (MCMC) estimation of SNP effects can be quite time consuming or slow to converge when a large number of SNPs are fitted simultaneously in a linear mixed model. Here we present an EM algorithm (termed “fastBayesA”) without MCMC. This fastBayesA approach treats the variances of SNP effects as missing data and uses a joint posterior mode of effects compared to the commonly used BayesA which bases predictions on posterior means of effects. In each EM iteration, SNP effects are predicted as a linear combination of best linear unbiased predictions of breeding values from a mixed linear animal model that incorporates a weighted marker-based realized relationship matrix. Method fastBayesA converges after a few iterations to a joint posterior mode of SNP effects under the BayesA model. When applied to simulated quantitative traits with a range of genetic architectures, fastBayesA is shown to predict GEBV as accurately as BayesA but with less computing effort per SNP than BayesA. Method fastBayesA can be used as a computationally efficient substitute for BayesA, especially when an increasing number of markers bring unreasonable computational burden or slow convergence to MCMC approaches. 相似文献
995.
S Agampodi T Agampodi N Wickramasinghe S Fernando U Chathurani W Adhikari I Dharshika D Nugegoda S Dharmaratne D Newlands 《PloS one》2012,7(8):e42333
Background
The global impact of maternal ill health on economic productivity is estimated to be over 15 billion USD per year. Global data on productivity cost associated with maternal ill health are limited to estimations based on secondary data. Purpose of our study was to determine the productivity cost due to maternal ill health during pregnancy in Sri Lanka.Methods and Findings
We studied 466 pregnant women, aged 24 to 36 weeks, residing in Anuradhapura, Sri Lanka. A two stage cluster sampling procedure was used in a cross sectional design and all pregnant women were interviewed at clinic centers, using the culturally adapted Immpact tool kit for productivity cost assessment. Of the 466 pregnant women studied, 421 (90.3%) reported at least one ill health condition during the pregnancy period, and 353 (83.8%) of them had conditions affecting their daily life. Total incapacitation requiring another person to carry out all their routine activities was reported by 122 (26.1%) of the women. In this study sample, during the last episode of ill health, total number of days lost due to absenteeism was 3,356 (32.9% of total loss) and the days lost due to presenteeism was 6,832.8 (67.1% of the total loss). Of the 353 women with ill health conditions affecting their daily life, 280 (60%) had coping strategies to recover loss of productivity. Of the coping strategies used to recover productivity loss during maternal ill health, 76.8% (n = 215) was an intra-household adaptation, and 22.8% (n = 64) was through social networks. Loss of productivity was 28.9 days per episode of maternal ill health. The mean productivity cost due to last episode of ill health in this sample was Rs.8,444.26 (95% CI-Rs.6888.74-Rs.9999.78).Conclusions
Maternal ill health has a major impact on household productivity and economy. The major impact is due to, generally ignored minor ailments during pregnancy. 相似文献996.
Objectives
The World Health Organization considers Cesarean section rates of 5–15% to be the optimal range for targeted provision of this life saving intervention. However, access to safe Cesarean section in resource-limited settings is much lower, estimated at 1–2% reported in sub-Saharan Africa. This study reports Cesarean sections rates and indications in Democratic Republic of Congo, Burundi, and Sierra Leone, and describe the main parameters associated with maternal and early neonatal mortality.Methods
Women undergoing Cesarean section from August 1 2010 to January 31 2011 were included in this prospective study. Logistic regression was used to model determinants of maternal and early neonatal mortality.Results
1276 women underwent a Cesarean section, giving a frequency of 6.2% (range 4.1–16.8%). The most common indications were obstructed labor (399, 31%), poor presentation (233, 18%), previous Cesarean section (184, 14%), and fetal distress (128, 10%), uterine rupture (117, 9%) and antepartum hemorrhage (101, 8%). Parity >6 (adjusted odds ratio [aOR] = 8.6, P = 0.015), uterine rupture (aOR = 20.5; P = .010), antepartum hemorrhage (aOR = 13.1; P = .045), and pre-eclampsia/eclampsia (aOR = 42.9; P = .017) were associated with maternal death. Uterine rupture (aOR = 6.6, P<0.001), anterpartum hemorrhage (aOR = 3.6, P<0.001), and cord prolapse (aOR = 2.7, P = 0.017) were associated with early neonatal death.Conclusions
This study demonstrates that target Cesarean section rates can be achieved in sub-Saharan Africa. Identifying the common indications for Cesarean section and associations with mortality can target improvements in antenatal services and emergency obstetric care. 相似文献997.
LF Hernandez-Zimbron J Luna-Muñoz R Mena R Vazquez-Ramirez C Kubli-Garfias DH Cribbs K Manoutcharian G Gevorkian 《PloS one》2012,7(8):e42344
Extracellular and intraneuronal accumulation of amyloid-beta aggregates has been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of amyloid-beta neurotoxicity is not completely understood. Previous studies suggest that binding of amyloid-beta to a number of macromolecules has deleterious effects on cellular functions. Mitochondria were found to be the target for amyloid-beta, and mitochondrial dysfunction is well documented in AD. In the present study we have shown for the first time that Aβ 1-42 bound to a peptide comprising the amino-terminal region of cytochrome c oxidase subunit 1. Phage clone, selected after screening of a human brain cDNA library expressed on M13 phage and bearing a 61 amino acid fragment of cytochrome c oxidase subunit 1, bound to Aβ 1-42 in ELISA as well as to Aβ aggregates present in AD brain. Aβ 1-42 and cytochrome c oxidase subunit 1 co-immunoprecipitated from mitochondrial fraction of differentiated human neuroblastoma cells. Likewise, molecular dynamics simulation of the cytochrome c oxidase subunit 1 and the Aβ 1-42 peptide complex resulted in a reliable helix-helix interaction, supporting the experimental results. The interaction between Aβ 1-42 and cytochrome c oxidase subunit 1 may explain, in part, the diminished enzymatic activity of respiratory chain complex IV and subsequent neuronal metabolic dysfunction observed in AD. 相似文献
998.
999.
D Coggon G Ntani KT Palmer VE Felli R Harari LH Barrero SA Felknor D Gimeno A Cattrell C Serra M Bonzini E Solidaki E Merisalu RR Habib F Sadeghian M Kadir SS Warnakulasuriya K Matsudaira B Nyantumbu MR Sim H Harcombe K Cox MH Marziale LM Sarquis F Harari R Freire N Harari MV Monroy LA Quintana M Rojas EJ Salazar Vega EC Harris S Vargas-Prada JM Martinez G Delclos FG Benavides M Carugno MM Ferrario AC Pesatori L Chatzi P Bitsios M Kogevinas K Oha T Sirk A Sadeghian RJ Peiris-John N Sathiakumar 《PloS one》2012,7(7):e39820
Background
The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample.Methods/Principal Findings
A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as “repetitive strain injury” (RSI).Conclusions/Significance
The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively. 相似文献1000.
Francesco Di Domenico Fernando Lucchese Donatella Magri 《Perspectives in Plant Ecology, Evolution and Systematics》2012,14(5):354-362
The suggested location of broadleaved evergreen trees in Europe during the last full-glacial has traditionally favoured a southerly refugial model, which proposes survival in the Mediterranean peninsulas and recolonization of central and northern Europe during the Holocene. This hypothesis is not always substantiated by thorough reviews of original past and modern occurrence data, or considered in the light of plant traits and autoecology. Our approach focuses on the genus Buxus with the aim of exploring (i) the relationship between the location of refugia and post-glacial population dynamics, (ii) past processes determining density, fragmentation and local extinctions of modern populations, and (iii) the vulnerability of Buxus in the context of the undergoing environmental changes. We compiled a database of over 3600 modern occurrences and 676 fossil sites to reconstruct the distribution of Buxus in Europe since 30 ka cal BP. The location of fossil finds and the plant traits of Buxus indicate that it persisted widely across its modern distribution through the last glacial period with modes varying from region to region. The E Pyrenees, W Alps, and Jura Mts hosted dense populations, which expanded exponentially during the whole Holocene, and resulted in a modern continuous distribution area. In contrast, the Mediterranean Peninsulas hosted sparse populations, which increased exponentially only during the first half of the Holocene, clearly decreased in the last 4.5 ka BP and resulted in a highly fragmented modern distribution area, most likely in relation to the climate trends towards dry conditions of the last few millennia. These results challenge the common view that the Mediterranean regions are the exclusive and most important refuge areas for evergreen broadleaved trees and stress the importance of considering long-term population dynamics based on fossil data to evaluate the vulnerability of modern fragmented plant populations in view of conservation actions. 相似文献