全文获取类型
收费全文 | 5953篇 |
免费 | 415篇 |
国内免费 | 3篇 |
出版年
2023年 | 50篇 |
2022年 | 96篇 |
2021年 | 151篇 |
2020年 | 123篇 |
2019年 | 127篇 |
2018年 | 173篇 |
2017年 | 149篇 |
2016年 | 253篇 |
2015年 | 363篇 |
2014年 | 389篇 |
2013年 | 451篇 |
2012年 | 548篇 |
2011年 | 485篇 |
2010年 | 291篇 |
2009年 | 226篇 |
2008年 | 337篇 |
2007年 | 334篇 |
2006年 | 283篇 |
2005年 | 259篇 |
2004年 | 226篇 |
2003年 | 209篇 |
2002年 | 158篇 |
2001年 | 71篇 |
2000年 | 48篇 |
1999年 | 63篇 |
1998年 | 46篇 |
1997年 | 41篇 |
1996年 | 40篇 |
1995年 | 29篇 |
1994年 | 33篇 |
1993年 | 31篇 |
1992年 | 43篇 |
1991年 | 17篇 |
1990年 | 21篇 |
1989年 | 16篇 |
1988年 | 23篇 |
1987年 | 14篇 |
1986年 | 13篇 |
1985年 | 12篇 |
1984年 | 12篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 8篇 |
1977年 | 16篇 |
1976年 | 5篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1972年 | 5篇 |
排序方式: 共有6371条查询结果,搜索用时 15 毫秒
111.
Chi Song Gary K. Chen Robert C. Millikan Christine B. Ambrosone Esther M. John Leslie Bernstein Wei Zheng Jennifer J. Hu Regina G. Ziegler Sarah Nyante Elisa V. Bandera Sue A. Ingles Michael F. Press Sandra L. Deming Jorge L. Rodriguez-Gil Stephen J. Chanock Peggy Wan Xin Sheng Loreall C. Pooler David J. Van Den Berg Loic Le Marchand Laurence N. Kolonel Brian E. Henderson Chris A. Haiman Daniel O. Stram 《PloS one》2013,8(2)
Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density. 相似文献
112.
Paulo Ricardo Porfírio do Nascimento Daniella Regina Arantes Martins Glória Regina Góis Monteiro Paula Vivianne Queiroz Francisco Paulo Freire-Neto José Wilton Queiroz ádila Lorena Morais Lima Selma Maria Bezerra Jeronimo 《PloS one》2013,8(10)
Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection. 相似文献
113.
Kátia Regina da Silva Roberto Costa Elizabeth Sartori Crevelari Marianna Sobral Lacerda Caio Marcos de Moraes Albertini Martino Martinelli Filho José Eduardo Santana Jo?o Ricardo Nickenig Vissoci Ricardo Pietrobon Jacson V. Barros 《PloS one》2013,8(7)
Background
The ability to apply standard and interoperable solutions for implementing and managing medical registries as well as aggregate, reproduce, and access data sets from legacy formats and platforms to advanced standard formats and operating systems are crucial for both clinical healthcare and biomedical research settings.Purpose
Our study describes a reproducible, highly scalable, standard framework for a device registry implementation addressing both local data quality components and global linking problems.Methods and Results
We developed a device registry framework involving the following steps: (1) Data standards definition and representation of the research workflow, (2) Development of electronic case report forms using REDCap (Research Electronic Data Capture), (3) Data collection according to the clinical research workflow and, (4) Data augmentation by enriching the registry database with local electronic health records, governmental database and linked open data collections, (5) Data quality control and (6) Data dissemination through the registry Web site. Our registry adopted all applicable standardized data elements proposed by American College Cardiology / American Heart Association Clinical Data Standards, as well as variables derived from cardiac devices randomized trials and Clinical Data Interchange Standards Consortium. Local interoperability was performed between REDCap and data derived from Electronic Health Record system. The original data set was also augmented by incorporating the reimbursed values paid by the Brazilian government during a hospitalization for pacemaker implantation. By linking our registry to the open data collection repository Linked Clinical Trials (LinkedCT) we found 130 clinical trials which are potentially correlated with our pacemaker registry.Conclusion
This study demonstrates how standard and reproducible solutions can be applied in the implementation of medical registries to constitute a re-usable framework. Such approach has the potential to facilitate data integration between healthcare and research settings, also being a useful framework to be used in other biomedical registries. 相似文献114.
Rodrigo R. de Oliveira Concei??o S. Martins Yuri R. Rocha Allysson B. R. Braga R?mulo M. Mattos Fábio Hecht Gerly A. C. Brito Luiz E. Nasciutti 《PloS one》2013,8(10)
This study aims to demonstrate how the state of chronic hyperglycemia from experimental Diabetes Mellitus can influence the homeostatic imbalance of tendons and, consequently, lead to the characteristics of tendinopathy. Twenty animals were randomly divided into two experimental groups: control group, consisting of healthy rats and diabetic group constituted by rats induced to Diabetes Mellitus I. After twenty-four days of the induction of Diabetes type I, the Achilles tendon were removed for morphological evaluation, cellularity, number and cross-sectional area of blood vessel, immunohistochemistry for Collagen type I, VEGF and NF-κB nuclear localization sequence (NLS) and nitrate and nitrite level. The Achilles tendon thickness (µm/100g) of diabetic animals was significantly increased and, similarly, an increase was observed in the density of fibrocytes and mast cells in the tendons of the diabetic group. The average number of blood vessels per field, in peritendinous tissue, was statistically higher in the diabetic group 3.39 (2.98) vessels/field when compared to the control group 0.89 (1.68) vessels/field p = 0.001 and in the intratendinous region, it was observed that blood vessels were extremely rare in the control group 0.035 (0.18) vessels/field and were often present in the tendons of the diabetic group 0.89 (0.99) vessels/field. The immunohistochemistry analysis identified higher density of type 1 collagen and increased expression of VEGF as well as increased immunostaining for NFκB p50 NLS in the nucleus in Achilles tendon of the diabetic group when compared to the control group. Higher levels of nitrite/nitrate were observed in the experimental group induced to diabetes. We conclude that experimental DM induces notable structural, inflammatory and vascular changes in the Achilles tendon which are compatible with the process of chronic tendinopathy. 相似文献
115.
Simona Nardozza Helen L. Boldingh M. Peggy Kashuba Regina Feil Dan Jones Amali H. Thrimawithana Hilary S. Ireland Marine Philippe Mark W. Wohlers Tony K. McGhie Mirco Montefiori John E. Lunn Andrew C. Allan Annette C. Richardson 《Plant, cell & environment》2020,43(4):819-835
Kiwifruit (Actinidia spp.) is a recently domesticated fruit crop with several novel-coloured cultivars being developed. Achieving uniform fruit flesh pigmentation in red genotypes is challenging. To investigate the cause of colour variation between fruits, we focused on a red-fleshed Actinidia chinensis var. chinensis genotype. It was hypothesized that carbohydrate supply could be responsible for this variation. Early in fruit development, we imposed high or low (carbon starvation) carbohydrate supplies treatments; carbohydrate import or redistribution was controlled by applying a girdle at the shoot base. Carbon starvation affected fruit development as well as anthocyanin and carbohydrate metabolite concentrations, including the signalling molecule trehalose 6-phosphate. RNA-Seq analysis showed down-regulation of both gene-encoding enzymes in the anthocyanin and carbohydrate biosynthetic pathways. The catalytic trehalose 6-phosphate synthase gene TPS1.1a was down-regulated, whereas putative regulatory TPS7 and TPS11 were strongly up-regulated. Unexpectedly, under carbon starvation MYB10, the anthocyanin pathway regulatory activator was slightly up-regulated, whereas MYB27 was also up-regulated and acts as a repressor. To link these two metabolic pathways, we propose a model where trehalose 6-phosphate and the active repressor MYB27 are involved in sensing the carbon starvation status. This signals the plant to save resources and reduce the production of anthocyanin in fruits. 相似文献
116.
Leandro Nolé Eduardo Michael Maia Mincarone Flávia Lucena-Frédou Júlia Rodrigues Martins Gabriel Vinícius Felix Afonso Bárbara Teixeira Villarins Thierry Frédou Alex Souza Lira Arnaud Bertrand 《Zeitschrift fur angewandte Ichthyologie》2020,36(6):845-848
Length-weight relationship parameters were calculated for twelve mesopelagic fish species from the western Tropical Atlantic: Diretmus argenteus, Melamphaes polylepis, Bolinichthys distofax, Diaphus lucidus, Diaphus splendidus, Electrona risso, Hygophum taaningi, Taaningichthys bathyphilus, Melanolagus bericoides, Winteria telescopa, Diplophos taenia, Astronesthes similus. Data was collected off northeastern Brazil from April 9th to May 6th, 2017. Hauls were conducted during day and night at 47 stations by using a micronekton trawl (body mesh: 40 mm, cod-end mesh: 10 mm) from 10 to 1,113 m depth. The material was fixed in a 4% formalin solution for 1 month and then preserved in a 70% alcohol solution for proximally 6 months before processing for length (nearest 0.1 cm of standard length) and weight (nearest 0.01 g of total weight). A new maximum standard length for Winteria telescopa is also provided. 相似文献
117.
118.
Amanda Carolina Borges da Silva Janaina de Cassia Orlandi Sardi Daniella Gorete Lourenço de Oliveira Caio Fernando Ramalho de Oliveira Helder Freitas dos Santos Edson Lucas dos Santos 《Biofouling》2020,36(5):516-527
AbstractCandida yeast infections are the fourth leading cause of death worldwide. Peptides with antimicrobial activity are a promising alternative treatment for such infections. Here, the antifungal activity of a new antimicrobial peptide—PEP-IA18—was evaluated against Candida species. PEP-IA18 was designed from the primary sequence of profilin, a protein from Spodoptera frugiperda, and displayed potent activity against Candida albicans and Candida tropicalis, showing a minimum inhibitory concentration (MIC) of 2.5?µM. Furthermore, the mechanism of action of PEP-IA18 involved interaction with the cell membrane (ergosterol complexation). Treatment at MIC and/or 10?×?MIC significantly reduced biofilm formation and viability. PEP-IA18 showed low toxicity toward human fibroblasts and only revealed hemolytic activity at high concentrations. Thus, PEP-IA18 exhibited antifungal and anti-biofilm properties with potential applicability in the treatment of infections caused by Candida species. 相似文献
119.
Jesualdo A. Fuentes-G. Paul David Polly Emília P. Martins 《Evolution; international journal of organic evolution》2020,74(2):311-325
Phylogenetic comparative methods use tree topology, branch lengths, and models of phenotypic change to take into account nonindependence in statistical analysis. However, these methods normally assume that trees and models are known without error. Approaches relying on evolutionary regimes also assume specific distributions of character states across a tree, which often result from ancestral state reconstructions that are subject to uncertainty. Several methods have been proposed to deal with some of these sources of uncertainty, but approaches accounting for all of them are less common. Here, we show how Bayesian statistics facilitates this task while relaxing the homogeneous rate assumption of the well-known phylogenetic generalized least squares (PGLS) framework. This Bayesian formulation allows uncertainty about phylogeny, evolutionary regimes, or other statistical parameters to be taken into account for studies as simple as testing for coevolution in two traits or as complex as testing whether bursts of phenotypic change are associated with evolutionary shifts in intertrait correlations. A mixture of validation approaches indicates that the approach has good inferential properties and predictive performance. We provide suggestions for implementation and show its usefulness by exploring the coevolution of ankle posture and forefoot proportions in Carnivora. 相似文献
120.
Aureo Banhos Bruno L. Fontes Débora Regina Yogui Mario Henrique Alves Natália Carneiro Ardente Renata Valls Lucas Mendes Barreto Lucas Damásio Átilla Colombo Ferreguetti Andréa Siqueira Carvalho Vitor Roberto Schettino Alexandre Rosa dos Santos Helena Godoy Bergallo Ana Carolina Srbek-Araujo Emilia Patrícia Medici Ariel Canena Arnaud L.J. Desbiez 《Biotropica》2020,52(3):421-426
We report 24 records of giant armadillo roadkill on Brazilian highways in the Cerrado, Pantanal and Amazon biomes illustrating that highways are a threat to this species. However, we also documented the species using underpasses, demonstrating that these structures could help to reduce the risk of roadkill for giant armadillos. 相似文献