全文获取类型
收费全文 | 1667篇 |
免费 | 133篇 |
国内免费 | 2篇 |
专业分类
1802篇 |
出版年
2023年 | 13篇 |
2022年 | 36篇 |
2021年 | 62篇 |
2020年 | 26篇 |
2019年 | 37篇 |
2018年 | 32篇 |
2017年 | 41篇 |
2016年 | 36篇 |
2015年 | 89篇 |
2014年 | 78篇 |
2013年 | 97篇 |
2012年 | 146篇 |
2011年 | 128篇 |
2010年 | 91篇 |
2009年 | 58篇 |
2008年 | 85篇 |
2007年 | 104篇 |
2006年 | 77篇 |
2005年 | 74篇 |
2004年 | 60篇 |
2003年 | 59篇 |
2002年 | 64篇 |
2001年 | 14篇 |
2000年 | 21篇 |
1999年 | 19篇 |
1998年 | 14篇 |
1997年 | 16篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 6篇 |
1992年 | 9篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1987年 | 8篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 12篇 |
1981年 | 14篇 |
1979年 | 8篇 |
1976年 | 6篇 |
1975年 | 4篇 |
1974年 | 6篇 |
1973年 | 8篇 |
1972年 | 5篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1967年 | 4篇 |
排序方式: 共有1802条查询结果,搜索用时 12 毫秒
101.
Robert Chizimba Nicola Christofides Tobias Chirwa Isaac Singini Chineme Ozumba Simon Sikwese Hastings T. Banda Rhoda Banda Henry Chimbali Bagrey Ngwira Alister Munthali Peter Nyasulu 《PloS one》2015,10(4)
Background
Tuberculosis (TB) is one of the main causes of death in developing countries. Awareness and perception of risk of TB could influence early detection, diagnosis and care seeking at treatment centers. However, perceptions about TB are influenced by sources of information.Aim
This study aimed to determine the association between multiple sources of information, and perceptions of risk of TB among adults aged 18–49 years.Methods
A cross-sectional study was conducted in Ntcheu district in Malawi. A total of 121 adults were sampled in a three-stage simple random sampling technique. Data were collected using a structured questionnaire. Perceptions of risk were measured using specific statements that reflected common myths and misconceptions. Low risk perception implied a person having strong belief in myths and misconceptions about TB and high risk perception meant a person having no belief in myths or misconceptions and demonstrated understanding of the disease.Results
Females were more likely to have low risk perceptions about TB compared to males (67.7% vs. 32.5%, p = 0.01). The higher the household asset index the more likely an individual had higher risk perceptions about TB (p = 0.006). The perception of risk of TB was associated with sources of information (p = 0.03). Use of both interpersonal communication and mass media was 2.8 times more likely to be associated with increased perception of risk of TB (Odds Ratio [OR] = 2.8; 95% Confidence interva1[CI]: 3.1–15. 6; p = 0.01). After adjusting for sex and asset ownership, use of interpersonal communication and mass media were more likely to be associated with higher perception of risk of TB (OR, 2.0; 95% CI: 1.65–10.72; p = 0.003) compared with interpersonal communication only (OR 1.6, 95%; CI: 1.13–8.98, p = 0.027).Conclusion
The study found that there was association between multiple sources of information, and higher perceptions of risk of TB among adults aged 18–49 years. 相似文献102.
Kabemba E. Mwape Joachim Blocher Jasmin Wiefek Kathie Schmidt Pierre Dorny Nicolas Praet Clarance Chiluba Holger Schmidt Isaac K. Phiri Andrea S. Winkler Sarah Gabri?l 《PLoS neglected tropical diseases》2015,9(8)
Zambia is endemic for Taenia solium taeniosis and cysticercosis. In this single-centered, cross-sectional, community-based study, the role of neurocysticercosis (NCC) as a cause of epilepsy was examined. People with epilepsy (PWE, n = 56) were identified in an endemic area using a screening questionnaire followed by in-depth interviews and neurological examination. Computed tomography (CT) was performed on 49 people with active epilepsy (PWAE) and their sera (specific antibody and antigen detection, n = 56) and stools (copro-antigen detection, n = 54) were analyzed. The CT scan findings were compared to a group of 40 CT scan controls. Of the PWE, 39.3% and 23.2% were positive for cysticercal antibodies and antigens, respectively, and 14.8% for coproantigens (taeniosis). Lesions highly suggestive of NCC were detected in 24.5% and definite NCC lesions in 4.1% of CT scans of PWAE. This compares to 2.5% and 0%, respectively, in the control CT scans. Using the Del Brutto diagnostic criteria, 51.8% of the PWAE were diagnosed with probable or definitive NCC and this rose to 57.1% when the adapted criteria, as proposed by Gabriël et al. (adding the sero-antigen ELISA test as a major criterion), were used. There was no statistically significant relationship between NCC, current age, age at first seizure and gender. This study suggests that NCC is the single most important cause of epilepsy in the study area. Additional large-scale studies, combining a community based prevalence study for epilepsy with neuroimaging and serological analysis in different areas are needed to estimate the true impact of neurocysticercosis in endemic regions and efforts should be instituted to the control of T. solium. 相似文献
103.
Tess V. Clendenen Justin Rendleman Wenzhen Ge Karen L. Koenig Isaac Wirgin Diane Currie Roy E. Shore Tomas Kirchhoff Anne Zeleniuch-Jacquotte 《PloS one》2015,10(8)
Background
Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA.Methods
We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women’s Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison.Results
We observed that 60 of the 81 SNPs (74%) had high call frequencies (≥95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping.Conclusions
Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies. 相似文献104.
Michal Mokry Harma Feitsma Isaac J. Nijman Ewart de Bruijn Pieter J. van der Zaag Victor Guryev Edwin Cuppen 《Nucleic acids research》2010,38(10):e116
Microarray-based enrichment of selected genomic loci is a powerful method for genome complexity reduction for next-generation sequencing. Since the vast majority of exons in vertebrate genomes are smaller than 150 nt, we explored the use of short fragment libraries (85–110 bp) to achieve higher enrichment specificity by reducing carryover and adverse effects of flanking intronic sequences. High enrichment specificity (60–75%) was obtained with a relative even base coverage. Up to 98% of the target-sequence was covered more than 20× at an average coverage depth of about 200×. To verify the accuracy of SNP/mutation detection, we evaluated 384 known non-reference SNPs in the targeted regions. At ∼200× average sequence coverage, we were able to survey 96.4% of 1.69 Mb of genomic sequence with only 4.2% false negative calls, mostly due to low coverage. Using the same settings, a total of 1197 novel candidate variants were detected. Verification experiments revealed only eight false positive calls, indicating an overall false positive rate of less than 1 per ∼200 000 bp. Taken together, short fragment libraries provide highly efficient and flexible enrichment of exonic targets and yield relatively even base coverage, which facilitates accurate SNP and mutation detection. Raw sequencing data, alignment files and called SNPs have been submitted into GEO database http://www.ncbi.nlm.nih.gov/geo/ with accession number . GSE18542相似文献
105.
Alison J. Kriegel Yi Fang Yong Liu Zhongmin Tian Domagoj Mladinov Isaac R. Matus Xiaoqiang Ding Andrew S. Greene Mingyu Liang 《Nucleic acids research》2010,38(22):8338-8347
We reported previously an approach for identifying microRNA (miRNA)-target pairs by combining miRNA and proteomic analyses. The approach was applied in the present study to examine human renal epithelial cells treated with transforming growth factor β1 (TGFβ1), a model of epithelial–mesenchymal transition important for the development of renal interstitial fibrosis. Treatment of human renal epithelial cells with TGFβ1 resulted in upregulation of 16 miRNAs and 18 proteins and downregulation of 17 miRNAs and 16 proteins. Of the miRNAs and proteins that exhibited reciprocal changes in expression, 77 pairs met the sequence criteria for miRNA–target interactions. Knockdown of miR-382, which was up-regulated by TGFβ1, attenuated TGFβ1-induced loss of the epithelial marker E-cadherin. miR-382 was confirmed by 3′-untranslated region reporter assay to target five genes that were downregulated at the protein level by TGFβ1, including superoxide dismutase 2 (SOD2). Knockdown of miR-382 attenuated TGFβ1-induced downregulation of SOD2. Overexpression of SOD2 ameliorated TGFβ1-induced loss of the epithelial marker. The study provided experimental evidence in the form of reciprocal expression at the protein level for a large number of predicted miRNA-target pairs and discovered a novel role of miR-382 and SOD2 in the loss of epithelial characteristics induced by TGFβ1. 相似文献
106.
107.
Thomas P. Matthews Tatiana McHardy Suki Klair Kathy Boxall Martin Fisher Michael Cherry Charlotte E. Allen Glynn J. Addison John Ellard G. Wynne Aherne Isaac M. Westwood Rob van Montfort Michelle D. Garrett John C. Reader Ian Collins 《Bioorganic & medicinal chemistry letters》2010,20(14):4045-4049
A range of 3,6-di(hetero)arylimidazo[1,2-a]pyrazine ATP-competitive inhibitors of CHK1 were developed by scaffold hopping from a weakly active screening hit. Efficient synthetic routes for parallel synthesis were developed to prepare analogues with improved potency and ligand efficiency against CHK1. Kinase profiling showed that the imidazo[1,2-a]pyrazines could inhibit other kinases, including CHK2 and ABL, with equivalent or better potency depending on the pendant substitution. These 3,6-di(hetero)aryl imidazo[1,2-a]pyrazines appear to represent a general kinase inhibitor scaffold. 相似文献
108.
Isaac Wirgin Cheryl Grunwald Joseph Stabile John R. Waldman 《Conservation Genetics》2010,11(3):689-708
Shortnose sturgeon Acipenser brevirostrum is federally listed as ‘‘an endangered species threatened with extinction’’ in the U.S. but its listing status is currently
under review. As part of this process, the U.S. National Marine Fisheries Service will determine if shortnose sturgeon are
divided into Distinct Population Segments (DPS) across its distribution. In this regard, we sought to determine if shortnose
sturgeon occur in genetically “discrete population segments,” and if so, the boundaries of each. We used mitochondrial DNA
(mtDNA) control region sequence analysis to assess the genetic discreteness of 14 of 19 river populations that were recommended
as DPS in the 1998 Final Recovery Plan for Shortnose Sturgeon. Nine of the 14 proposed DPS proved significantly discrete (P < 0.05 after Bonferoni correction) from both of their bracketing populations, the exceptions being those in the Penobscot
River, Chesapeake Bay, Cooper River, and Ogeechee River (our sample from the Cape Fear River was insufficient to statistically
analyze). Haplotype frequencies in the newly “rediscovered” Penobscot River collection were almost identical to those in the
proximal Kennebec River system. Genetic data in combination with tagging results suggest that shortnose sturgeon in the Penobscot
River are probably migrants from the Kennebec. Likewise, shortnose sturgeon found today within the Chesapeake Bay appear to
be migrants from the Delaware River. While haplotype frequencies in the remnant Santee River population in Lake Marion differed
significantly from those in nearby Winyah Bay, they did not differ significantly from those in the Cooper River. This suggests
that the Cooper River harbors descendants of the Santee River population that are unable to access their historical spawning
locales. The Ogeechee River collection was not genetically distinct from that in the nearby Savannah River, suggesting that
it may host descendants of hatchery-reared individuals of Savannah River ancestry. Our genetic results indicate that most,
but not all, rivers with shortnose sturgeon host genetically discrete populations, constituting important information in the
consideration of DPS designations. However, shortnose sturgeon migrations through coastal waters to proximal rivers and release
of hatchery-reared fish may confound results from genetic studies such as ours and lead to the possible misidentification
of discrete population segments. 相似文献
109.
Diap Graciela Amuasi John Boakye Isaac Sevcsik Ann-Marie Pecoul Bernard 《Malaria journal》2010,9(1):1-11
Background
Malaria microscopy and rapid diagnostic tests are insensitive for very low-density parasitaemia. This insensitivity may lead to missed asymptomatic sub-microscopic parasitaemia, a potential reservoir for infection. Similarly, mixed infections and interactions between Plasmodium species may be missed. The objectives were first to develop a rapid and sensitive PCR-based diagnostic method to detect low parasitaemia and mixed infections, and then to investigate the epidemiological importance of sub-microscopic and mixed infections in Rattanakiri Province, Cambodia.Methods
A new malaria diagnostic method, using restriction fragment length polymorphism analysis of the cytochrome b genes of the four human Plasmodium species and denaturing high performance liquid chromatography, has been developed. The results of this RFLP-dHPLC method have been compared to 1) traditional nested PCR amplification of the 18S rRNA gene, 2) sequencing of the amplified fragments of the cytochrome b gene and 3) microscopy. Blood spots on filter paper and Giemsa-stained blood thick smears collected in 2001 from 1,356 inhabitants of eight villages of Rattanakiri Province have been analysed by the RFLP-dHPLC method and microscopy to assess the prevalence of sub-microscopic and mixed infections.Results
The sensitivity and specificity of the new RFLP-dHPLC was similar to that of the other molecular methods. The RFLP-dHPLC method was more sensitive and specific than microscopy, particularly for detecting low-level parasitaemia and mixed infections. In Rattanakiri Province, the prevalences of Plasmodium falciparum and Plasmodium vivax were approximately two-fold and three-fold higher, respectively, by RFLP-dHPLC (59% and 15%, respectively) than by microscopy (28% and 5%, respectively). In addition, Plasmodium ovale and Plasmodium malariae were never detected by microscopy, while they were detected by RFLP-dHPLC, in 11.2% and 1.3% of the blood samples, respectively. Moreover, the proportion of mixed infections detected by RFLP-dHPLC was higher (23%) than with microscopy (8%).Conclusions
The rapid and sensitive molecular diagnosis method developed here could be considered for mass screening and ACT treatment of inhabitants of low-endemicity areas of Southeast Asia. 相似文献110.
Tibor Kiss Krisztina Balla Ottó Veisz László Láng Zoltán Bedő Simon Griffiths Peter Isaac Ildikó Karsai 《Molecular breeding : new strategies in plant improvement》2014,34(2):297-310
Heading of cereals is determined by complex genetic and environmental factors in which genes responsible for vernalization and photoperiod sensitivity play a decisive role. Our aim was to use diagnostic molecular markers to determine the main allele types in VRN-A1, VRN-B1, VRN-D1, PPD-B1 and PPD-D1 in a worldwide wheat collection of 683 genotypes and to investigate the effect of these alleles on heading in the field. The dominant VRN-A1, VRN-B1 and VRN-D1 alleles were present at a low frequency. The PPD-D1a photoperiod-insensitive allele was carried by 57 % of the cultivars and was most frequent in Asian and European cultivars. The PPD-B1 photoperiod-insensitive allele was carried by 22 % of the genotypes from Asia, America and Europe. Nine versions of the PPD-B1-insensitive allele were identified based on gene copy number and intercopy structure. The allele compositions in PPD-D1, PPD-B1 and VRN-D1 significantly influenced heading and together explained 37.5 % of the phenotypic variance. The role of gene model increased to 39.1 % when PPD-B1 intercopy structure was taken into account instead of overall PPD-B1 type (sensitive vs. insensitive). As a single component, PPD-D1 had the most important role (28.0 % of the phenotypic variance), followed by PPD-B1 (12.3 % for PPD-B1_overall, and 15.1 % for PPD-B1_intercopy) and VRN-D1 (2.2 %). Significant gene interactions were identified between the marker alleles within PPD-B1 and between VRN-D1 and the two PPD1 genes. The earliest heading genotypes were those with the photoperiod-insensitive allele in PPD-D1 and PPD-B1, and with the spring allele for VRN-D1 and the winter alleles for VRN-A1 and VRN-B1. This combination could only be detected in genotypes from Southern Europe and Asia. Late-heading genotypes had the sensitivity alleles for both PPD1 genes, regardless of the allelic composition of the VRN1 genes. There was a 10-day difference in heading between the earliest and latest groups under field conditions. 相似文献