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Watson GE Lynch M Myers GJ Shamlaye CF Thurston SW Zareba G Clarkson TW Davidson PW 《Journal of the American Dental Association (1939)》2011,142(11):1283-1294
BackgroundDental amalgams contain approximately 50 percent metallic mercury and emit mercury vapor during the life of the restoration. Controversy surrounds whether fetal exposure to mercury vapor resulting from maternal dental amalgam restorations has neurodevelopmental consequences.MethodsThe authors determined maternal amalgam restoration status during gestation (prenatal exposure to mercury vapor [Hg0]) retrospectively in 587 mother-child pairs enrolled in the Seychelles Child Development Study, a prospective longitudinal cohort study of the effects of prenatal and recent postnatal methylmercury (MeHg) exposure on neurodevelopment. They examined covariate-adjusted associations between prenatal maternal amalgam restoration status and the results of six age-appropriate neurodevelopmental tests administered at age 66 months. The authors fit the models without and with adjustment for prenatal and recent postnatal MeHg exposure metrics.ResultsThe mean number of maternal amalgam restorations present during gestation was 5.1 surfaces (range, 1–22) in the 42.4 percent of mothers who had amalgam restorations. The authors found no significant adverse associations between the number of amalgam surfaces present during gestation and any of the six outcomes, with or without adjustment for prenatal and postnatal MeHg exposure. Results of analyses with the secondary metric, prenatal amalgam occlusal point scores, showed an adverse association in boys only on a letter- and word-identification subtest of a frequently used test of scholastic achievement, whereas girls scored better on several other tests with increasing exposure.ConclusionsThis study’s results provide no support for the hypothesis that prenatal Hg0 exposure arising from maternal dental amalgam restorations results in neurobehavioral consequences in the child. These findings require confirmation from a prospective study of coexposure to MeHg and Hg0. 相似文献
83.
Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review 总被引:1,自引:0,他引:1
Aurélie Roux Dominique Lison Christophe Junot Jean-François Heilier 《Clinical biochemistry》2011,(1):119-135
The metabolome is the set of small molecular mass organic compounds found in a given biological media. It includes all organic substances naturally occurring from the metabolism of the studied living organism, except biological polymers, but also xenobiotics and their biotransformation products. The metabolic fingerprints of biofluids obtained by mass spectrometry (MS) or nuclear magnetic resonance (NMR)-based methods contain a few hundreds to thousands of signals related to both genetic and environmental contributions. Metabolomics, which refers to the untargeted quantitative or semi-quantitative analysis of the metabolome, is a promising tool for biomarker discovery. Although proof-of-concept studies by metabolomics-based approaches in the field of toxicology and clinical chemistry have initially been performed using NMR, the use of liquid chromatography hyphenated to mass spectrometry (LC/MS) has increased over the recent years, providing complementary results to those obtained with other approaches. This paper reviews and comments the input of LC/MS in this field. We describe here the overall process of analysis, review some seminal papers in the field and discuss the perspectives of metabolomics for the biomonitoring of exposure and diagnosis of diseases. 相似文献
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目的:参考顾客满意度指数模型建立社区中医药服务公众满意度结构方程模型,以广州?深圳?汕头?惠州和湛江5个城市为例,对广东省社区中医药服务现状进行分析?方法:以偏最小二乘法(PLS)为拟合方法,开展广东省社区中医药服务公众满意度的实证研究?结果:广东省社区中医药服务公众满意度结构方程模型拟合度理想,具有可行性?结论:针对测评结果提出要进一步推动社区公众满意度测评,提高社区中医药服务的综合质量,改善影响满意度的重要因素 相似文献
86.
Geser F Prvulovic D O'Dwyer L Hardiman O Bede P Bokde AL Trojanowski JQ Hampel H 《Progress in neurobiology》2011,95(4):649-662
Pathological 43-kDa transactive response sequence DNA-binding protein (TDP-43) has been recognized as the major disease protein in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin positive, tau and α-synuclein negative inclusions (FTLD-U) and the transitional forms between these multisystem conditions. In order to develop TDP-43 into a successful ALS biomarker, the natural history of TDP-43 pathology needs to be characterized and the underlying pathophysiology established. Here we propose a spatial and temporal "two-axes" model of central nervous system vulnerability for TDP-43 linked degeneration and review recent studies on potential biomarkers related to pathological TDP-43 in the cerebrospinal fluid (CSF), blood, and skeletal muscle. The model includes the following two arms: Firstly, a "motor neuron disease" or "spinal cord/brainstem to motor cortex" axis (with degeneration possibly ascending from the lower motor neurons to the upper motor neurons); and secondly, a "dementia" or "corticoid/allocortex to neocortex" axis (with a probable spread of TDP-43 linked degeneration from the mediotemporal lobe to wider mesocortical and neocortical brain areas). At the cellular level, there is a gradual disappearance of normal TDP-43 in the nucleus in combination with the formation of pathological aggregates in the cell body and cellular processes, which can also be used to identify the stage of the disease process. Moreover, TDP-43 lesions in subpial/subependymal or perivascular localizations have been noted, and this might account for increased CSF and blood TDP-43 levels through mechanisms that remain to be elucidated. 相似文献
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A comprehensive Quality by Design development paradigm should consider the impact of raw materials and formulation on the final drug product. This work proposes a quantitative approach to simultaneously predict particle, powder, and compact mechanical properties of a pharmaceutical blend, based on that of the raw materials. A new, two-step, multivariate modeling method, referred to as the weighted scores PLS, was developed to address the challenge of predicting the properties of a powder blend while enabling process understanding. The model validation exercise is shown along with selected practical applications. It is shown how the proposed in-silico model exhibits sufficient predictive power to be an important tool in the pharmaceutical development decision making process while requiring minimal experimentation and material usage. 相似文献
90.
Nelson C.N. Chan Kin-Mang Lau Kelvin C. K. Cheng Natalie P.H. Chan Margaret H.L. Ng 《Hemoglobin》2016,40(6):400-404
Genetic association studies showed that Hb F is under the influence of major quantitative trait loci (QTL) in β-thalassemia (β-thal) carriers. Single nucleotide polymorphisms (SNPs) at three major QTLs, BCL11A, HBS1L-MYB intergenic region and XmnI-HBG2 were individually validated in univariate models. However, their relative effect sizes on Hb F regulation are unknown. We genotyped 99 Chinese β-thal carriers for the three major QTLs and performed genetic association studies using three different statistical models, including mass univariate analysis, multivariate linear regression and partial least square regression structural equation modeling (PLS-SEM). Performances of the three models were compared and effect sizes of the three QTLs in a multivariate model were assessed. Traditional mass univariate analysis and multivariate linear regression showed limited statistical power in our small cohort and the latter was constrained by multicollinearity. Partial least structural equation modeling showed significant positive associations of each QTL (p?<0.05) with Hb F regulation, together explained 34.4% of variance. The HBS1L-MYB intergenic region polymorphism (HMIP) demonstrated the highest effect on Hb F prediction with effect size f2 0.294. PLS-SEM offered a statistically powerful multivariate model for multi-locus genetic association studies. We reproduced findings of previous studies with a much smaller cohort and demonstrated HMIP as the strongest regulator of Hb F in Chinese β-thal carriers. 相似文献