全文获取类型
收费全文 | 7006篇 |
免费 | 650篇 |
国内免费 | 3篇 |
专业分类
7659篇 |
出版年
2022年 | 64篇 |
2021年 | 130篇 |
2020年 | 79篇 |
2019年 | 85篇 |
2018年 | 100篇 |
2017年 | 88篇 |
2016年 | 160篇 |
2015年 | 304篇 |
2014年 | 300篇 |
2013年 | 454篇 |
2012年 | 551篇 |
2011年 | 499篇 |
2010年 | 305篇 |
2009年 | 252篇 |
2008年 | 426篇 |
2007年 | 423篇 |
2006年 | 382篇 |
2005年 | 321篇 |
2004年 | 311篇 |
2003年 | 313篇 |
2002年 | 311篇 |
2001年 | 101篇 |
2000年 | 67篇 |
1999年 | 94篇 |
1998年 | 93篇 |
1997年 | 64篇 |
1996年 | 66篇 |
1995年 | 52篇 |
1994年 | 63篇 |
1993年 | 50篇 |
1992年 | 49篇 |
1991年 | 46篇 |
1990年 | 55篇 |
1989年 | 37篇 |
1988年 | 38篇 |
1987年 | 32篇 |
1986年 | 40篇 |
1985年 | 48篇 |
1984年 | 45篇 |
1983年 | 42篇 |
1982年 | 42篇 |
1981年 | 42篇 |
1980年 | 34篇 |
1978年 | 32篇 |
1977年 | 27篇 |
1976年 | 33篇 |
1975年 | 29篇 |
1974年 | 30篇 |
1973年 | 29篇 |
1969年 | 25篇 |
排序方式: 共有7659条查询结果,搜索用时 11 毫秒
301.
Manuel Quirós Rubén Martínez-Moreno Joan Albiol Pilar Morales Felícitas Vázquez-Lima Antonio Barreiro-Vázquez Pau Ferrer Ramon Gonzalez 《PloS one》2013,8(8)
As a consequence of the increase in global average temperature, grapes with the adequate phenolic and aromatic maturity tend to be overripe by the time of harvest, resulting in increased sugar concentrations and imbalanced C/N ratios in fermenting musts. This fact sets obvious additional hurdles in the challenge of obtaining wines with reduced alcohols levels, a new trend in consumer demands. It would therefore be interesting to understand Saccharomyces cerevisiae physiology during the fermentation of must with these altered characteristics. The present study aims to determine the distribution of metabolic fluxes during the yeast exponential growth phase, when both carbon and nitrogen sources are in excess, using continuous cultures. Two different sugar concentrations were studied under two different winemaking temperature conditions. Although consumption and production rates for key metabolites were severely affected by the different experimental conditions studied, the general distribution of fluxes in central carbon metabolism was basically conserved in all cases. It was also observed that temperature and sugar concentration exerted a higher effect on the pentose phosphate pathway and glycerol formation than on glycolysis and ethanol production. Additionally, nitrogen uptake, both quantitatively and qualitatively, was strongly influenced by environmental conditions. This work provides the most complete stoichiometric model used for Metabolic Flux Analysis of S. cerevisiae in wine fermentations employed so far, including the synthesis and release of relevant aroma compounds and could be used in the design of optimal nitrogen supplementation of wine fermentations. 相似文献
302.
Luis Alberto Henríquez-Hernández Almudena Valenciano Palmira Foro-Arnalot María Jesús álvarez-Cubero José Manuel Cozar José Francisco Suárez-Novo Manel Castells-Esteve Adriana Ayala-Gil Pablo Fernández-Gonzalo Montse Ferrer Ferrán Guedea Gemma Sancho-Pardo Jordi Craven-Bartle María José Ortiz-Gordillo Patricia Cabrera-Roldán Estefanía Herrera-Ramos Pedro C. Lara 《PloS one》2013,8(7)
Background
Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics.Objective
To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias.Design, Setting, and Participants
A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArray® NT Cycler.Outcome Measurements and Statistical Analysis
Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer.Results and Limitations
We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics.Conclusion
Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out. 相似文献303.
Gemma Moncunill Alfredo Mayor Azucena Bardají Laura Puyol Augusto Nhabomba Diana Barrios Ruth Aguilar María-Jesús Pinazo Mercè Almirall Cristina Soler José Mu?oz Joaquim Gascón Carlota Doba?o 《PloS one》2013,8(8)
Immunity to malaria is believed to wane with time in the absence of exposure to Plasmodium falciparum infection, but immunoepidemiological data on longevity of immunity remain controversial. We quantified serum cytokines and chemokines by suspension array technology as potential biomarkers for durability of immunity in immigrants with clinical malaria after years without parasite exposure. These were compared to serum/plasma profiles in naïve adults (travelers) and semi-immune adults under continuous exposure, with malaria, along with immigrant and traveler patients without malaria. Immigrants had higher levels of IL-2, IL-5 and IL-8 compared to semi-immune adults with malaria (P≤0.0200). Time since immigration correlated with increased IL-2 (rho=0.2738P=0.0495) and IFN-γ (rho=0.3044P=0.0282). However, immigrants did not show as high IFN-γ concentrations as travelers during a first malaria episode (P<0.0001). Immigrants and travelers with malaria had higher levels of IFN-γ, IL-6, and IL-10 (P<0.0100) than patients with other diseases, and IL-8 and IL-1β were elevated in immigrants with malaria (P<0.0500). Therefore, malaria patients had a characteristic strong pro-inflammatory/Th1 signature. Upon loss of exposure, control of pro-inflammatory responses and tolerance to P. falciparum appeared to be reduced. Understanding the mechanisms to maintain non-pathogenic effector responses is important to develop new malaria control strategies. 相似文献
304.
Estimating the success of enzyme bioprospecting through metagenomics: current status and future trends 下载免费PDF全文
Manuel Ferrer Mónica Martínez‐Martínez Rafael Bargiela Wolfgang R. Streit Olga V. Golyshina Peter N. Golyshin 《Microbial biotechnology》2016,9(1):22-34
Recent reports have suggested that the establishment of industrially relevant enzyme collections from environmental genomes has become a routine procedure. Across the studies assessed, a mean number of approximately 44 active clones were obtained in an average size of approximately 53 000 clones tested using naïve screening protocols. This number could be significantly increased in shorter times when novel metagenome enzyme sequences obtained by direct sequencing are selected and subjected to high‐throughput expression for subsequent production and characterization. The pre‐screening of clone libraries by naïve screens followed by the pyrosequencing of the inserts allowed for a 106‐fold increase in the success rate of identifying genes encoding enzymes of interest. However, a much longer time, usually on the order of years, is needed from the time of enzyme identification to the establishment of an industrial process. If the hit frequency for the identification of enzymes performing at high turnover rates under real application conditions could be increased while still covering a high natural diversity, the very expensive and time‐consuming enzyme optimization phase would likely be significantly shortened. At this point, it is important to review the current knowledge about the success of fine‐tuned naïve‐ and sequence‐based screening protocols for enzyme selection and to describe the environments worldwide that have already been subjected to enzyme screen programmes through metagenomic tools. Here, we provide such estimations and suggest the current challenges and future actions needed before environmental enzymes can be successfully introduced into the market. 相似文献
305.
NIH working group report—using genomic information to guide weight management: From universal to precision treatment 下载免费PDF全文
306.
307.
Christina Ahlstrom Herman W. Barkema Karen Stevenson Ruth N. Zadoks Roman Biek Rowland Kao Hannah Trewby Deb Haupstein David F. Kelton Gilles Fecteau Olivia Labrecque Greg P. Keefe Shawn L. B. McKenna Kapil Tahlan Jeroen De Buck 《PloS one》2016,11(2)
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative bacterium of Johne’s disease (JD) in ruminants. The control of JD in the dairy industry is challenging, but can be improved with a better understanding of the diversity and distribution of MAP subtypes. Previously established molecular typing techniques used to differentiate MAP have not been sufficiently discriminatory and/or reliable to accurately assess the population structure. In this study, the genetic diversity of 182 MAP isolates representing all Canadian provinces was compared to the known global diversity, using single nucleotide polymorphisms identified through whole genome sequencing. MAP isolates from Canada represented a subset of the known global diversity, as there were global isolates intermingled with Canadian isolates, as well as multiple global subtypes that were not found in Canada. One Type III and six “Bison type” isolates were found in Canada as well as one Type II subtype that represented 86% of all Canadian isolates. Rarefaction estimated larger subtype richness in Québec than in other Canadian provinces using a strict definition of MAP subtypes and lower subtype richness in the Atlantic region using a relaxed definition. Significant phylogeographic clustering was observed at the inter-provincial but not at the intra-provincial level, although most major clades were found in all provinces. The large number of shared subtypes among provinces suggests that cattle movement is a major driver of MAP transmission at the herd level, which is further supported by the lack of spatial clustering on an intra-provincial scale. 相似文献
308.
Ruth R. Miller Miguel Uyaguari-Diaz Mark N. McCabe Vincent Montoya Jennifer L. Gardy Shoshana Parker Theodore Steiner William Hsiao Matthew J. Nesbitt Patrick Tang David M. Patrick for the CCD Study Group 《PloS one》2016,11(11)
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease causing indefinite fatigue. ME/CFS has long been hypothesised to have an infectious cause; however, no specific infectious agent has been identified. We used metagenomics to analyse the RNA from plasma samples from 25 individuals with ME/CFS and compare their microbial content to technical controls as well as three control groups: individuals with alternatively diagnosed chronic Lyme syndrome (N = 13), systemic lupus erythematosus (N = 11), and healthy controls (N = 25). We found that the majority of sequencing reads were removed during host subtraction, thus there was very low microbial RNA content in the plasma. The effects of sample batching and contamination during sample processing proved to outweigh the effects of study group on microbial RNA content, as the few differences in bacterial or viral RNA abundance we did observe between study groups were most likely caused by contamination and batch effects. Our results highlight the importance of including negative controls in all metagenomic analyses, since there was considerable overlap between bacterial content identified in study samples and control samples. For example, Proteobacteria, Firmicutes, Actinobacteria, and Bacteriodes were found in both study samples and plasma-free negative controls. Many of the taxonomic groups we saw in our plasma-free negative control samples have previously been associated with diseases, including ME/CFS, demonstrating how incorrect conclusions may arise if controls are not used and batch effects not accounted for. 相似文献
309.
Jose L. López-Campos Maria Abad Arranz Carmen Calero-Acu?a Fernando Romero-Valero Ruth Ayerbe-García Antonio Hidalgo-Molina Ricardo I. Aguilar-Pérez-Grovas Francisco García-Gil Francisco Casas-Maldonado Laura Caballero-Ballesteros María Sánchez-Palop Dolores Pérez-Tejero Alejandro Segado Jose Calvo-Bonachera Bárbara Hernández-Sierra Adolfo Doménech Macarena Arroyo-Varela Francisco González-Vargas Juan J. Cruz-Rueda 《PloS one》2016,11(3)