全文获取类型
收费全文 | 6915篇 |
免费 | 561篇 |
国内免费 | 7篇 |
出版年
2023年 | 43篇 |
2022年 | 79篇 |
2021年 | 257篇 |
2020年 | 126篇 |
2019年 | 176篇 |
2018年 | 176篇 |
2017年 | 131篇 |
2016年 | 257篇 |
2015年 | 392篇 |
2014年 | 397篇 |
2013年 | 481篇 |
2012年 | 602篇 |
2011年 | 575篇 |
2010年 | 360篇 |
2009年 | 295篇 |
2008年 | 411篇 |
2007年 | 375篇 |
2006年 | 314篇 |
2005年 | 304篇 |
2004年 | 309篇 |
2003年 | 258篇 |
2002年 | 296篇 |
2001年 | 49篇 |
2000年 | 38篇 |
1999年 | 54篇 |
1998年 | 39篇 |
1997年 | 46篇 |
1996年 | 36篇 |
1995年 | 26篇 |
1994年 | 28篇 |
1993年 | 27篇 |
1992年 | 34篇 |
1991年 | 16篇 |
1990年 | 19篇 |
1989年 | 16篇 |
1988年 | 13篇 |
1987年 | 20篇 |
1986年 | 14篇 |
1985年 | 21篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 12篇 |
1981年 | 22篇 |
1980年 | 16篇 |
1978年 | 14篇 |
1976年 | 11篇 |
1975年 | 14篇 |
1974年 | 12篇 |
1973年 | 11篇 |
1966年 | 13篇 |
排序方式: 共有7483条查询结果,搜索用时 109 毫秒
141.
142.
Carrie B. Moore John R. Wallace Daniel J. Wolfe Alex T. Frase Sarah A. Pendergrass Kenneth M. Weiss Marylyn D. Ritchie 《PLoS genetics》2013,9(12)
Analyses investigating low frequency variants have the potential for explaining additional genetic heritability of many complex human traits. However, the natural frequencies of rare variation between human populations strongly confound genetic analyses. We have applied a novel collapsing method to identify biological features with low frequency variant burden differences in thirteen populations sequenced by the 1000 Genomes Project. Our flexible collapsing tool utilizes expert biological knowledge from multiple publicly available database sources to direct feature selection. Variants were collapsed according to genetically driven features, such as evolutionary conserved regions, regulatory regions genes, and pathways. We have conducted an extensive comparison of low frequency variant burden differences (MAF<0.03) between populations from 1000 Genomes Project Phase I data. We found that on average 26.87% of gene bins, 35.47% of intergenic bins, 42.85% of pathway bins, 14.86% of ORegAnno regulatory bins, and 5.97% of evolutionary conserved regions show statistically significant differences in low frequency variant burden across populations from the 1000 Genomes Project. The proportion of bins with significant differences in low frequency burden depends on the ancestral similarity of the two populations compared and types of features tested. Even closely related populations had notable differences in low frequency burden, but fewer differences than populations from different continents. Furthermore, conserved or functionally relevant regions had fewer significant differences in low frequency burden than regions under less evolutionary constraint. This degree of low frequency variant differentiation across diverse populations and feature elements highlights the critical importance of considering population stratification in the new era of DNA sequencing and low frequency variant genomic analyses. 相似文献
143.
Mohlopheni J. Marakalala Simon Vautier Joanna Potrykus Louise A. Walker Kelly M. Shepardson Alex Hopke Hector M. Mora-Montes Ann Kerrigan Mihai G. Netea Graeme I. Murray Donna M. MacCallum Robert Wheeler Carol A. Munro Neil A. R. Gow Robert A. Cramer Alistair J. P. Brown Gordon D. Brown 《PLoS pathogens》2013,9(4)
144.
Seok-Hyung Kim Sarah A. Scott Michael J. Bennett Robert P. Carson Joshua Fessel H. Alex Brown Kevin C. Ess 《PLoS genetics》2013,9(6)
Multiple Acyl-CoA Dehydrogenase Deficiency (MADD) is a severe mitochondrial disorder featuring multi-organ dysfunction. Mutations in either the ETFA, ETFB, and ETFDH genes can cause MADD but very little is known about disease specific mechanisms due to a paucity of animal models. We report a novel zebrafish mutant dark xavier (dxavu463) that has an inactivating mutation in the etfa gene. dxavu463 recapitulates numerous pathological and biochemical features seen in patients with MADD including brain, liver, and kidney disease. Similar to children with MADD, homozygote mutant dxavu463 zebrafish have a spectrum of phenotypes ranging from moderate to severe. Interestingly, excessive maternal feeding significantly exacerbated the phenotype. Homozygous mutant dxavu463 zebrafish have swollen and hyperplastic neural progenitor cells, hepatocytes and kidney tubule cells as well as elevations in triacylglycerol, cerebroside sulfate and cholesterol levels. Their mitochondria were also greatly enlarged, lacked normal cristae, and were dysfunctional. We also found increased signaling of the mechanistic target of rapamycin complex 1 (mTORC1) with enlarged cell size and proliferation. Treatment with rapamycin partially reversed these abnormalities. Our results indicate that etfa gene function is remarkably conserved in zebrafish as compared to humans with highly similar pathological, biochemical abnormalities to those reported in children with MADD. Altered mTORC1 signaling and maternal nutritional status may play critical roles in MADD disease progression and suggest novel treatment approaches that may ameliorate disease severity. 相似文献
145.
Raquel Montero Manuela Grazina Ester López-Gallardo Julio Montoya Paz Briones Aleix Navarro-Sastre John M. Land Iain P. Hargreaves Rafael Artuch Maria del Mar O'Callaghan Cristina Jou Cecilia Jimenez Nuria Buján Mercè Pineda Angels García-Cazorla Andrés Nascimento Plácido Navas 《Mitochondrion》2013,13(4):337-341
We evaluated coenzyme Q10 (CoQ) levels in patients studied under suspicion of mitochondrial DNA depletion syndromes (MDS) (n = 39). CoQ levels were quantified by HPLC, and the percentage of mtDNA depletion by quantitative real-time PCR. A high percentage of MDS patients presented with CoQ deficiency as compared to other mitochondrial patients (Mann–Whitney-U test: p = 0.001). Our findings suggest that MDS are frequently associated with CoQ deficiency, as a possible secondary consequence of disease pathophysiology. Assessment of muscle CoQ status seems advisable in MDS patients since the possibility of CoQ supplementation may then be considered as a candidate therapy. 相似文献
146.
Jotham Suez Steffen Porwollik Amir Dagan Alex Marzel Yosef Ilan Schorr Prerak T. Desai Vered Agmon Michael McClelland Galia Rahav Ohad Gal-Mor 《PloS one》2013,8(3)
Human infection with non-typhoidal Salmonella serovars (NTS) infrequently causes invasive systemic disease and bacteremia. To understand better the nature of invasive NTS (iNTS), we studied the gene content and the pathogenicity of bacteremic strains from twelve serovars (Typhimurium, Enteritidis, Choleraesuis, Dublin, Virchow, Newport, Bredeney, Heidelberg, Montevideo, Schwarzengrund, 9,12:l,v:- and Hadar). Comparative genomic hybridization using a Salmonella enterica microarray revealed a core of 3233 genes present in all of the iNTS strains, which include the Salmonella pathogenicity islands 1–5, 9, 13, 14; five fimbrial operons (bcf, csg, stb, sth, sti); three colonization factors (misL, bapA, sinH); and the invasion gene, pagN. In the iNTS variable genome, we identified 16 novel genomic islets; various NTS virulence factors; and six typhoid-associated virulence genes (tcfA, cdtB, hlyE, taiA, STY1413, STY1360), displaying a wider distribution among NTS than was previously known. Characterization of the bacteremic strains in C3H/HeN mice showed clear differences in disease manifestation. Previously unreported characterization of serovars Schwarzengrund, 9,12:l,v:-, Bredeney and Virchow in the mouse model showed low ability to elicit systemic disease, but a profound and elongated shedding of serovars Schwarzengrund and 9,12:l,v:- (as well as Enteritidis and Heidelberg) due to chronic infection of the mouse. Phenotypic comparison in macrophages and epithelial cell lines demonstrated a remarkable intra-serovar variation, but also showed that S. Typhimurium bacteremic strains tend to present lower intracellular growth than gastroenteritis isolates. Collectively, our data demonstrated a common core of virulence genes, which might be required for invasive salmonellosis, but also an impressive degree of genetic and phenotypic heterogeneity, highlighting that bacteremia is a complex phenotype, which cannot be attributed merely to an enhanced invasion or intracellular growth of a particular strain. 相似文献
147.
Sophie Githinji Samwel Kigen Dorothy Memusi Andrew Nyandigisi Agneta M. Mbithi Andrew Wamari Alex N. Muturi George Jagoe Jim Barrington Robert W. Snow Dejan Zurovac 《PloS one》2013,8(1)
Background
Health facility stock-outs of life saving malaria medicines are common across Africa. Innovative ways of addressing this problem are urgently required. We evaluated whether SMS based reporting of stocks of artemether-lumefantrine (AL) and rapid diagnostic tests (RDT) can result in reduction of stock-outs at peripheral facilities in Kenya.Methods/Findings
All 87 public health facilities in five Kenyan districts were included in a 26 week project. Weekly facility stock counts of four AL packs and RDTs were sent via structured incentivized SMS communication process from health workers’ personal mobile phones to a web-based system accessed by district managers. The mean health facility response rate was 97% with a mean formatting error rate of 3%. Accuracy of stock count reports was 79% while accuracy of stock-out reports was 93%. District managers accessed the system 1,037 times at an average of eight times per week. The system was accessed in 82% of the study weeks. Comparing weeks 1 and 26, stock-out of one or more AL packs declined by 38 percentage-points. Total AL stock-out declined by 5 percentage-points and was eliminated by the end of the project. Stock-out declines of individual AL packs ranged from 14 to 32 percentage-points while decline in RDT stock-outs was 24 percentage-points. District managers responded to 44% of AL and 73% of RDT stock-out signals by redistributing commodities between facilities. In comparison with national trends, stock-out declines in study areas were greater, sharper and more sustained.Conclusions
Use of simple SMS technology ensured high reporting rates of reasonably accurate, real-time facility stock data that were used by district managers to undertake corrective actions to reduce stock-outs. Future work on stock monitoring via SMS should focus on assessing response rates without use of incentives and demonstrating effectiveness of such interventions on a larger scale. 相似文献148.
Koen Peeters Grietens Joan Muela Ribera Veronica Soto Alex Tenorio Sarah Hoibak Angel Rosas Aguirre Elizabeth Toomer Hugo Rodriguez Alejandro Llanos Cuentas Umberto D'Alessandro Dionicia Gamboa Annette Erhart 《PloS one》2013,8(1)
Background
While coverage of long-lasting insecticide-treated nets (LLIN) has steadily increased, a growing number of studies report gaps between net ownership and use. We conducted a mixed-methods social science study assessing the importance of net preference and use after Olyset® LLINs were distributed through a mass campaign in rural communities surrounding Iquitos, the capital city of the Amazonian region of Peru.Methods
The study was conducted in the catchment area of the Paujil and Cahuide Health Centres (San Juan district) between July 2007 and November 2008. During a first qualitative phase, participant observation and in-depth interviews collected information on key determinants for net preference and use. In a second quantitative phase, a survey among recently confirmed malaria patients evaluated the acceptability and use of both LLINs and traditional nets, and a case control study assessed the association between net preference/use and housing structure (open vs. closed houses).Results
A total of 10 communities were selected for the anthropological fieldwork and 228 households participated in the quantitative studies. In the study area, bed nets are considered part of the housing structure and are therefore required to fulfil specific architectural and social functions, such as providing privacy and shelter, which the newly distributed Olyset® LLINs ultimately did not. The LLINs'' failure to meet these criteria could mainly be attributed to their large mesh size, transparency and perceived ineffectiveness to protect against mosquitoes and other insects, resulting in 63.3% of households not using any of the distributed LLINs. Notably, LLIN usage was significantly lower in houses with no interior or exterior walls (35.2%) than in those with walls (73.8%) (OR = 5.2, 95CI [2.2; 12.3], p<0.001).Conclusion
Net preference can interfere with optimal LLIN use. In order to improve the number of effective days of LLIN protection per dollar spent, appropriate quantitative and qualitative methods for collecting information on net preference should be developed before any LLIN procurement decision is made. 相似文献149.
150.
Alex F?rster Hans Ulrich Kerl Holger Wenz Marc A. Brockmann Ingo N?lte Christoph Groden 《PloS one》2013,8(10)