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81.
Cdric Annweiler Mlinda Beaudenon Jennifer Gautier Justine Gonsard Sophie Boucher Guillaume Chapelet Astrid Darsonval Bertrand Fougre Olivier Gurin Marjorie Houvet Pierre Mnager Claire Roubaud-Baudron Achille Tchalla Jean-Claude Souberbielle Jrmie Riou Elsa Parot-Schinkel Thomas Clarier 《PLoS medicine》2022,19(5)
BackgroundVitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).Methods and findingsThis multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study.ConclusionsIn this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days.Trial registrationClinicalTrials.gov .In a randomized trial, Cedric Annweiler and colleagues evaluate whether a single high dose of vitamin D3 improves survival among older adults in France with SARS-CoV-2 infection. NCT04344041相似文献
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84.
Sources of nitrate in rivers draining sixteen watersheds in the northeastern U.S.: Isotopic constraints 总被引:3,自引:4,他引:3
Mayer Bernhard Boyer Elizabeth W. Goodale Christine Jaworski Norbert A. van Breemen Nico Howarth Robert W. Seitzinger Sybil Billen Gilles Lajtha Kate Nadelhoffer Knute Van Dam Douwe Hetling Leo J. Nosal Miloslav Paustian Keith 《Biogeochemistry》2002,(1):171-197
The feasibility of using nitrogen and oxygenisotope ratios of nitrate (NO3
–) forelucidating sources and transformations ofriverine nitrate was evaluated in a comparativestudy of 16 watersheds in the northeastern U.S.A. Stream water was sampled repeatedly at theoutlets of the watersheds between January andDecember 1999 for determining concentrations,15N values, and 18Ovalues of riverine nitrate.In conjunction with information about land useand nitrogen fluxes,15Nnitrate and18Onitrate values providedmainly information about sources of riverinenitrate. In predominantly forested watersheds,riverine nitrate had mean concentrations ofless than 0.4 mg NO3
–-N L–1,15Nnitrate values of lessthan +5, and 18Onitratevalues between +12 and +19. This indicatesthat riverine nitrate was almost exclusivelyderived from soil nitrification processes withpotentially minor nitrate contributions fromatmospheric deposition in some catchments. Inwatersheds with significant agricultural andurban land use, concentrations of riverinenitrate were as high as 2.6 mg NO3
–-NL–1 with 15Nnitratevalues between +5 and +8 and18Onitrate values generallybelow +15. Correlations between nitrateconcentrations, 15Nnitratevalues, and N fluxes suggest that nitrate inwaste water constituted a major, and nitrate inmanure a minor additional source of riverinenitrate. Atmospheric nitrate deposition ornitrate-containing fertilizers were not asignificant source of riverine nitrate inwatersheds with significant agricultural andurban land use. Although complementary studiesindicate that in-stream denitrification wassignificant in all rivers, the isotopiccomposition of riverine nitrate sampled at theoutlet of the 16 watersheds did not provideevidence for denitrification in the form ofelevated 15Nnitrate and18Onitrate values. Relativelylow isotopic enrichment factors for nitrogenand oxygen during in-stream denitrification andcontinuous admixture of nitrate from theabove-described sources are thought to beresponsible for this finding. 相似文献
85.
Josette Garnier Aurélie Cébron Gaëlle Tallec Gilles Billen Mathieu Sebilo Anun Martinez 《Biogeochemistry》2006,77(3):305-326
The Seine River estuary (France) is the receptacle of a drainage basin characterised by high population density, heavy industrial
activity and intensive agriculture. Whereas nitrate concentrations are high due to diffuse sources in the upstream drainage
basin, ammonium mainly originates from the effluents of the Achères wastewater treatment plant (WWTP) downstream from Paris
and its suburbs (6.5 million equivalent-inhabitants). Ammonium is mostly nitrified in the tidal freshwater estuary and nitrification
causes a strong summer oxygen deficit. Average longitudinal summer profiles of oxygen and nitrogen concentrations for two
periods, between 1993–1997 and 1998–2003 in dry hydrological conditions (excluding the wet years 2000 and 2001) clearly reflect
the changes due to the improved treatment of wastewater from Paris and its suburbs. On the basis of daily water flux data
and twice monthly nitrogen measurements at the boundaries of the upstream freshwater estuarine section (108 km), we calculated
nitrification and denitrification fluxes, whose annual averages were 43 and 71 × 103 kg N d−1 respectively from 1993 to 2003, with summer values (July–September) representing 73 and 57% of the annual fluxes, respectively.
The degree of denitrification in the upper estuary appears to be closely related to the nitrification, itself more loosely
related to the amount of reduced nitrogen (Kjeldahl) brought by the treated effluents from the Achères WWTP. We estimated
the total N2O emissions to about 40 kg N d−1 (25–60 kg N d−1) in the same sector. 相似文献
86.
Glass TR Rotger M Telenti A Decosterd L Csajka C Bucher HC Günthard HF Rickenbach M Nicca D Hirschel B Bernasconi E Wandeler G Battegay M Marzolini C;Swiss HIV Cohort Study 《PloS one》2012,7(1):e29186
Background
Good adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels.Methods
Eligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA <400 copies/ml throughout the study period.Results
From January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01–0.99; LPV/r: OR 0.29, 95% CI: 0.09–0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62–18.75; LPV/r: OR 5.65, 95% CI: 1.82–17.56).Conclusions
The investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population. 相似文献87.
A unified framework to model the potential and realized distributions of invasive species within the invaded range 下载免费PDF全文
Tarek Hattab Carol X. Garzón‐López Michael Ewald Sandra Skowronek Raf Aerts Hélène Horen Boris Brasseur Emilie Gallet‐Moron Fabien Spicher Guillaume Decocq Hannes Feilhauer Olivier Honnay Pieter Kempeneers Sebastian Schmidtlein Ben Somers Ruben Van De Kerchove Duccio Rocchini Jonathan Lenoir 《Diversity & distributions》2017,23(7):806-819
88.
A Virulence and Antimicrobial Resistance DNA Microarray Detects a High Frequency of Virulence Genes in Escherichia coli Isolates from Great Lakes Recreational Waters 下载免费PDF全文
Katia Hamelin Guillaume Bruant Abdel El-Shaarawi Stephen Hill Thomas A. Edge Sadjia Bekal John Morris Fairbrother Jose Harel Christine Maynard Luke Masson Roland Brousseau 《Applied microbiology》2006,72(6):4200-4206
Escherichia coli is generally described as a commensal species with occasional pathogenic strains. Due to technological limitations, there is currently little information concerning the prevalence of pathogenic E. coli strains in the environment. For the first time, using a DNA microarray capable of detecting all currently described virulence genes and commonly found antimicrobial resistance genes, a survey of environmental E. coli isolates from recreational waters was carried out. A high proportion (29%) of 308 isolates from a beach site in the Great Lakes carried a pathotype set of virulence-related genes, and 14% carried antimicrobial resistance genes, findings consistent with a potential risk for public health. The results also showed that another 8% of the isolates had unusual virulence gene combinations that would be missed by conventional screening. This new application of a DNA microarray to environmental waters will likely have an important impact on public health, epidemiology, and microbial ecology in the future. 相似文献
89.
Mary Henry Noêmi GalAn Katherine Teasdale Renata Prado Harpreet Amar Marina S. Rays Lesley Roberts Pedro Siqueira Gilles de Wildt Marcos Virmond Pranab K. Das 《PLoS neglected tropical diseases》2016,10(3)
BackgroundLeprosy is a leading cause of preventable disability worldwide. Delay in diagnosis of patients augments the transmission of infection, and allows progression of disease and more severe disability. Delays in diagnosis greater than ten years have been reported in Brazil. To reduce this delay, it is important to identify factors that hinder patients from presenting to doctors, and those that delay doctors from diagnosing patients once they have presented. This study aimed to explore factors associated with the delayed diagnosis of leprosy in Brazil.
Methodology/ Principal Findings
This is an exploratory study using a self-constructed questionnaire delivered to patients attending three leprosy referral clinics across three states in Brazil. Data were analysed to determine associations between variables and the time taken for participants to present to the health-service, and between variables and the time taken for doctors to diagnose participants once they had presented. Participants who suspected they had leprosy but feared community isolation were 10 times more likely to wait longer before consulting a doctor for their symptoms (OR 10.37, 95% CI 2.18–49.45, p = 0.003). Participants who thought their symptoms were not serious had a threefold greater chance of waiting longer before consulting than those who did (OR 3.114, 95% CI 1.235–7.856, p = 0.016). Forty-two point six per cent of participants reported initially receiving a diagnosis besides leprosy. These had a three times greater chance of receiving a later diagnosis of leprosy compared to those not misdiagnosed or not given a diagnosis (OR 2.867, 95% CI 1.288–6.384, p = 0.010).Conclusions/ Significance
This study implies a need for patient education regarding leprosy symptoms and the reduction of stigma to encourage patients to present. The high rate of misdiagnosis reported suggests a need to increase clinician suspicion of leprosy. Further education regarding disease symptoms in medical school curriculums may be advisable. 相似文献90.
Froy O Zilberberg N Gordon D Turkov M Gilles N Stankiewicz M Pelhate M Loret E Oren DA Shaanan B Gurevitz M 《The Journal of biological chemistry》1999,274(9):5769-5776
Scorpion neurotoxins of the excitatory group show total specificity for insects and serve as invaluable probes for insect sodium channels. However, despite their significance and potential for application in insect-pest control, the structural basis for their bioactivity is still unknown. We isolated, characterized, and expressed an atypically long excitatory toxin, Bj-xtrIT, whose bioactive features resembled those of classical excitatory toxins, despite only 49% sequence identity. With the objective of clarifying the toxic site of this unique pharmacological group, Bj-xtrIT was employed in a genetic approach using point mutagenesis and biological and structural assays of the mutant products. A primary target for modification was the structurally unique C-terminal region. Sequential deletions of C-terminal residues suggested an inevitable significance of Ile73 and Ile74 for toxicity. Based on the bioactive role of the C-terminal region and a comparison of Bj-xtrIT with a Bj-xtrIT-based model of a classical excitatory toxin, AaHIT, a conserved surface comprising the C terminus is suggested to form the site of recognition with the sodium channel receptor. 相似文献