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991.
Tine Verreet Roel Quintens Debby Van Dam Mieke Verslegers Mirella Tanori Arianna Casciati Mieke Neefs Liselotte Leysen Arlette Michaux Ann Janssen Emiliano D’Agostino Greetje Vande Velde Sarah Baatout Lieve Moons Simonetta Pazzaglia Anna Saran Uwe Himmelreich Peter Paul De Deyn Mohammed Abderrafi Benotmane 《Journal of Neurodevelopmental Disorders》2015,7(1)
Background
In humans, in utero exposure to ionising radiation results in an increased prevalence of neurological aberrations, such as small head size, mental retardation and decreased IQ levels. Yet, the association between early damaging events and long-term neuronal anomalies remains largely elusive.Methods
Mice were exposed to different X-ray doses, ranging between 0.0 and 1.0 Gy, at embryonic days (E) 10, 11 or 12 and subjected to behavioural tests at 12 weeks of age. Underlying mechanisms of irradiation at E11 were further unravelled using magnetic resonance imaging (MRI) and spectroscopy, diffusion tensor imaging, gene expression profiling, histology and immunohistochemistry.Results
Irradiation at the onset of neurogenesis elicited behavioural changes in young adult mice, dependent on the timing of exposure. As locomotor behaviour and hippocampal-dependent spatial learning and memory were most particularly affected after irradiation at E11 with 1.0 Gy, this condition was used for further mechanistic analyses, focusing on the cerebral cortex and hippocampus. A classical p53-mediated apoptotic response was found shortly after exposure. Strikingly, in the neocortex, the majority of apoptotic and microglial cells were residing in the outer layer at 24 h after irradiation, suggesting cell death occurrence in differentiating neurons rather than proliferating cells. Furthermore, total brain volume, cortical thickness and ventricle size were decreased in the irradiated embryos. At 40 weeks of age, MRI showed that the ventricles were enlarged whereas N-acetyl aspartate concentrations and functional anisotropy were reduced in the cortex of the irradiated animals, indicating a decrease in neuronal cell number and persistent neuroinflammation. Finally, in the hippocampus, we revealed a reduction in general neurogenic proliferation and in the amount of Sox2-positive precursors after radiation exposure, although only at a juvenile age.Conclusions
Our findings provide evidence for a radiation-induced disruption of mouse brain development, resulting in behavioural differences. We propose that alterations in cortical morphology and juvenile hippocampal neurogenesis might both contribute to the observed aberrant behaviour. Furthermore, our results challenge the generally assumed view of a higher radiosensitivity in dividing cells. Overall, this study offers new insights into irradiation-dependent effects in the embryonic brain, of relevance for the neurodevelopmental and radiobiological field.Electronic supplementary material
The online version of this article (doi:10.1186/1866-1955-7-3) contains supplementary material, which is available to authorized users. 相似文献992.
993.
Enlarged meristems and delayed growth in plp mutants result from lack of CaaX prenyltransferases
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Running MP Lavy M Sternberg H Galichet A Gruissem W Hake S Ori N Yalovsky S 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(20):7815-7820
Meristems require a myriad of intercellular signaling pathways for coordination of cell division within and between functional zones and clonal cell layers. This control of cell division ensures a constant availability of stem cells throughout the life span of the meristem while limiting overproliferation of meristematic cells and maintaining the meristem structure. We have undertaken a genetic screen to identify additional components of meristem signaling pathways. We identified pluripetala (plp) mutants based on their dramatically larger meristems and increased floral organ number. PLURIPETALA encodes the alpha-subunit shared between protein farnesyltransferase and protein geranylgeranyltransferase-I. plp mutants also have altered abscisic acid responses and overall much slower growth rate. plp is epistatic to mutations in the beta-subunit of farnesyltransferase and shows a synergistic interaction with clavata3 mutants. plp mutants lead to insights into the mechanism of meristem homeostasis and provide a unique in vivo system for studying the functional role of prenylation in eukaryotes. 相似文献
994.
Cholesterol feeding of mice expressing cholesterol 7alpha-hydroxylase increases bile acid pool size despite decreased enzyme activity
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Tiemann M Han Z Soccio R Bollineni J Shefer S Sehayek E Breslow JL 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(7):1846-1851
Dietary cholesterol regulation of cholesterol 7alpha-hydroxylase (Cyp7a1), the rate-limiting enzyme in the classical pathway of bile acid synthesis, has been implicated in plasma cholesterol responsiveness. In the current study, the effects of 0.0% and 0.5% cholesterol diets were examined in Cyp7a1 knockout (KO), heterozygous Cyp7a1 KO (Het), and human Cyp7a1 transgenic mice on the mouse Cyp7a1 KO background (Tg+KO). We confirmed previous findings that dietary cholesterol increased mouse Cyp7a1 activity in Het mice but decreased human Cyp7a1 activity in Tg+KO mice. However, in both Het and Tg+KO mice, dietary cholesterol increased bile acid pool size (36% and 72%, respectively) and fecal bile acid excretion (2.2- and 3.6-fold, respectively). The expression of cholesterol 27-hydroxylase (Cyp27), the major enzyme of the alternative pathway of bile acid synthesis, was not significantly different in cholesterol-fed KO, Het, or Tg+KO mice. Furthermore, dietary cholesterol had comparable effects on total plasma cholesterol and non-high-density lipoprotein cholesterol in KO, Het, and Tg+KO mice. Thus, in Tg+KO mice, dietary cholesterol regulates bile acid pool size, fecal bile acid excretion, and plasma cholesterol independently of Cyp7a1 activity. These results challenge the notion that dietary cholesterol regulation of Cyp7a1 is a major determinant of plasma cholesterol responsiveness. 相似文献
995.
996.
Validation of the Social Appearance Anxiety Scale in Patients With Systemic Sclerosis: A Scleroderma Patient‐Centered Intervention Network Cohort Study
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Sarah D. Mills Linda Kwakkenbos Marie‐Eve Carrier Shadi Gholizadeh Rina S. Fox Lisa R. Jewett Karen Gottesman Scott C. Roesch Brett D. Thombs Vanessa L. Malcarne and the Scleroderma Patient‐centered Intervention Network Investigators 《Arthritis care & research》2018,70(10):1557-1562
Objective
Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes.Methods
Patients enrolled in the Scleroderma Patient‐centered Intervention Network Cohort completed the SAAS and measures of appearance‐related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple‐group CFA was used to determine whether SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size.Results
A total of 938 patients with SSc were included. CFA supported a 1‐factor structure (Comparative Fit Index 0.92, Standardized Root Mean Residual 0.04, and Root Mean Square Error of Approximation 0.08), and multiple‐group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = 0.96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression.Conclusion
The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes.997.
998.
999.
Effects of low dose metformin in adolescents with type I diabetes mellitus: a randomized,double‐blinded placebo‐controlled study
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1000.
Lois J. Surgenor Sarah Maguire Pierre J. V. Beumont 《European eating disorders review》2004,12(2):94-100
Despite renewed interest in drop‐out from eating disorders treatment, few studies have investigated the issue in respect to the most expensive and intensive form of treatment, that is, inpatient treatment for anorexia nervosa (AN). This study investigates whether risk of treatment drop‐out can be determined from information routinely collected at point of admission. Using information from a multi‐site database collected in Australia and New Zealand, demographic and clinical data at point of admission were collated for 213 inpatient treatment episodes. One in five admissions ended with the patient unilaterally deciding to leave treatment without clinician endorsement. A lower body mass index, AN purging subtype and active fluid restriction made significant independent contributions to this risk. Drop‐out remains a highly disruptive method of discharge and while there is utility in predicting those most at risk, few variables commonly collated by clinicians contribute to their identification. The implications for clinical practice and future research are discussed. Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association. 相似文献