全文获取类型
收费全文 | 7120篇 |
免费 | 705篇 |
国内免费 | 2篇 |
出版年
2022年 | 60篇 |
2021年 | 88篇 |
2020年 | 48篇 |
2019年 | 54篇 |
2018年 | 89篇 |
2017年 | 71篇 |
2016年 | 145篇 |
2015年 | 255篇 |
2014年 | 247篇 |
2013年 | 368篇 |
2012年 | 454篇 |
2011年 | 447篇 |
2010年 | 288篇 |
2009年 | 257篇 |
2008年 | 373篇 |
2007年 | 368篇 |
2006年 | 365篇 |
2005年 | 329篇 |
2004年 | 305篇 |
2003年 | 328篇 |
2002年 | 319篇 |
2001年 | 125篇 |
2000年 | 135篇 |
1999年 | 118篇 |
1998年 | 100篇 |
1997年 | 78篇 |
1996年 | 76篇 |
1995年 | 66篇 |
1994年 | 58篇 |
1993年 | 54篇 |
1992年 | 100篇 |
1991年 | 81篇 |
1990年 | 112篇 |
1989年 | 71篇 |
1988年 | 83篇 |
1987年 | 64篇 |
1986年 | 68篇 |
1985年 | 81篇 |
1984年 | 65篇 |
1983年 | 66篇 |
1982年 | 61篇 |
1981年 | 55篇 |
1980年 | 52篇 |
1979年 | 56篇 |
1978年 | 60篇 |
1977年 | 61篇 |
1976年 | 57篇 |
1975年 | 49篇 |
1974年 | 61篇 |
1972年 | 52篇 |
排序方式: 共有7827条查询结果,搜索用时 31 毫秒
991.
Francisco J. Román‐Dañobeytia Samuel I. Levy‐Tacher James Aronson Ricardo Ribeiro Rodrigues Jorge Castellanos‐Albores 《Restoration Ecology》2012,20(3):378-386
The rainforest of Mexico has been degraded and severely fragmented, and urgently require restoration. However, the practice of restoration has been limited by the lack of species‐specific data on survival and growth responses to local environmental variation. This study explores the differential performance of 14 wet tropical early‐, mid‐ or late‐successional tree species that were grown in two abandoned pastures with contrasting land‐use histories. After 18 months, seedling survival and growth of at least 7 of the 14 tree species studied were significantly higher in the site with a much longer history of land use (site 2). Saplings of the three early‐successional species showed exceptional growth rates. However, differences in performance were noted in relation to the differential soil properties between the experimental sites. Mid‐successional species generally showed slow growth rates but high seedling survival, whereas late‐successional species exhibited poor seedling survival at both the study sites. Stepwise linear regressions revealed that the species integrated response index combining survivorship and growth measurements, was influenced mostly by differences in soil pH between the two abandoned pastures. Our results suggest that local environmental variation among abandoned pastures of contrasting land‐use histories influences sapling survival and growth. Furthermore, the similarity of responses among species with the same successional status allowed us to make some preliminary site and species‐specific silvicultural recommendations. Future field experiments should extend the number of species and the range of environmental conditions to identify site “generalists” or more narrowly adapted species, that we would call “sensitive.” 相似文献
992.
L Gutknecht N Araragi S Merker J Waider FM Sommerlandt B Mlinar G Baccini U Mayer F Proft M Hamon AG Schmitt R Corradetti L Lanfumey KP Lesch 《PloS one》2012,7(8):e43157
Brain serotonin (5-HT) is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2). Tph2 inactivation (Tph2-/-) resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT) demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT(1A) and 5-HT(1B) receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis. 相似文献
993.
Background
The United States Public Health Service (USPHS) Guideline for Treating Tobacco Use and Dependence includes ten key recommendations regarding the identification and the treatment of tobacco users seen in all health care settings. To our knowledge, the impact of system-wide brief interventions with cigarette smokers on smoking prevalence and health care utilization has not been examined using patient population-based data.Methods and Findings
Data on clinical interventions with cigarette smokers were examined for primary care office visits of 104,639 patients at 17 Harvard Vanguard Medical Associates (HVMA) sites. An operational definition of “systems change” was developed. It included thresholds for intervention frequency and sustainability. Twelve sites met the criteria. Five did not. Decreases in self-reported smoking prevalence were 40% greater at sites that achieved systems change (13.6% vs. 9.7%, p<.01). On average, the likelihood of quitting increased by 2.6% (p<0.05, 95% CI: 0.1%–4.6%) per occurrence of brief intervention. For patients with a recent history of current smoking whose home site experienced systems change, the likelihood of an office visit for smoking-related diagnoses decreased by 4.3% on an annualized basis after systems change occurred (p<0.05, 95% CI: 0.5%–8.1%). There was no change in the likelihood of an office visit for smoking-related diagnoses following systems change among non-smokers.Conclusions
The clinical practice data from HVMA suggest that a systems approach can lead to significant reductions in smoking prevalence and the rate of office visits for smoking-related diseases. Most comprehensive tobacco intervention strategies focus on the provider or the tobacco user, but these results argue that health systems should be included as an integral component of a comprehensive tobacco intervention strategy. The HVMA results also give us an indication of the potential health impacts when meaningful use core tobacco measures are widely adopted. 相似文献994.
Bianca Bertulat Maria Luigia De Bonis Floriana Della Ragione Anne Lehmkuhl Manuela Milden Christian Storm K. Laurence Jost Simona Scala Brian Hendrich Maurizio D’Esposito M. Cristina Cardoso 《PloS one》2012,7(10)
The X-linked Mecp2 is a known interpreter of epigenetic information and mutated in Rett syndrome, a complex neurological disease. MeCP2 recruits HDAC complexes to chromatin thereby modulating gene expression and, importantly regulates higher order heterochromatin structure. To address the effects of MeCP2 deficiency on heterochromatin organization during neural differentiation, we developed a versatile model for stem cell in vitro differentiation. Therefore, we modified murine Mecp2 deficient (Mecp2
−/y) embryonic stem cells to generate cells exhibiting green fluorescent protein expression upon neural differentiation. Subsequently, we quantitatively analyzed heterochromatin organization during neural differentiation in wild type and in Mecp2 deficient cells. We found that MeCP2 protein levels increase significantly during neural differentiation and accumulate at constitutive heterochromatin. Statistical analysis of Mecp2 wild type neurons revealed a significant clustering of heterochromatin per nuclei with progressing differentiation. In contrast we found Mecp2 deficient neurons and astroglia cells to be significantly impaired in heterochromatin reorganization. Our results (i) introduce a new and manageable cellular model to study the molecular effects of Mecp2 deficiency, and (ii) support the view of MeCP2 as a central protein in heterochromatin architecture in maturating cells, possibly involved in stabilizing their differentiated state. 相似文献
995.
Vandrea Carla De Souza Muriel Rabilloud Pierre Cochat Luciano Selistre Aoumeur Hadj-Aissa Behrouz Kassai Bruno Ranchin Ulla Berg Maria Herthelius Laurence Dubourg 《PloS one》2012,7(12)
Background/Objective
Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population.Patients/Methods
We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort.Results
In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient.Conclusions
The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance. 相似文献996.
Kiss K Brozik A Kucsma N Toth A Gera M Berry L Vallentin A Vial H Vidal M Szakacs G 《PloS one》2012,7(5):e37378
ABCB6, a member of the adenosine triphosphate-binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria. 相似文献
997.
Hélène Marie Amélie Barrere Frédérique Schoentstein Marie-Hélène Chavanne Brigitte Grosgogeat Laurence Mora 《PloS one》2012,7(11)
Background
This study deals with the anchorage of polyelectrolyte films onto titanium surfaces via a cathecol-based linker for biomedical applications.Methodology
The following study uses a molecule functionalized with a catechol and a carboxylic acid: 3-(3,4-dihydroxyphenyl)propanoic acid. This molecule is anchored to the TiO2 substrate via the catechol while the carboxylic acid reacts with polymers bearing amine groups. By providing a film anchorage of chemisorption type, it makes possible to deposit polyelectrolytes on the surface of titanium.Principal Findings
Infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), contact angle and atomic force microscopy (AFM) measurements show that the different steps of grafting have been successfully performed.Conclusions
This method based on catechol anchorage of polyelectrolytes open a window towards large possibilities of clinical applications. 相似文献998.
S Le Vu A Velter L Meyer G Peytavin J Guinard J Pillonel F Barin C Semaille 《PloS one》2012,7(6):e39872
BACKGROUND: Population-based estimates of HIV incidence in France have revealed that men who have sex with men (MSM) are the most affected population and contribute to nearly half of new infections each year. We sought to estimate HIV incidence among sexually active MSM in Paris gay community social venues. METHODOLOGY/ PRINCIPAL FINDINGS: A cross-sectional survey was conducted in 2009 in a sample of commercial venues such as bars, saunas and backrooms. We collected a behavioural questionnaire and blood sample. Specimens were tested for HIV infection and positive specimens then tested for recent infection by the enzyme immunoassay for recent HIV-1 infection (EIA-RI). We assessed the presence of antiretroviral therapy among infected individuals to rule out treated patients in the algorithm that determined recent infection. Biomarker-based cross-sectional incidence estimates were calculated. We enrolled 886 MSM participants among which 157 (18%) tested HIV positive. In positive individuals who knew they were infected, 75% of EIA-RI positive results were due to ART. Of 157 HIV positive specimens, 15 were deemed to be recently infected. The overall HIV incidence was estimated at 3.8% person-years (py) [95%CI: 1.5-6.2]. Although differences were not significant, incidence was estimated to be 3.5% py [0.1-6.1] in men having had a negative HIV test in previous year and 4.8% py [0.1-10.6] in men having had their last HIV test more than one year before the survey, or never tested. Incidence was estimated at 4.1% py [0-8.3] in men under 35 years and 2.5% py [0-5.4] in older men. CONCLUSIONS/ SIGNIFICANCE: This is the first community-based survey to estimate HIV incidence among MSM in France. It includes ART detection and reveals a high level of HIV transmission in sexually active individuals, despite a high uptake of HIV testing. These data call for effective prevention programs targeting MSM engaged in high-risk behaviours. 相似文献
999.
1000.
Frange P Meyer L Deveau C Tran L Goujard C Ghosn J Girard PM Morlat P Rouzioux C Chaix ML;French ANRS CO PRIMO Cohort Study Group 《PloS one》2012,7(2):e31695