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41.
The regulation of neuropeptide gene expression and their receptors in a tissue specific and stimulus inducible manner will determine in part behaviour and physiology. This can be a dynamic process resulting from short term changes in response to the environment or long term modulation imposed by epigenetically determined mechanisms established during life experiences. The latter underpins what is termed ‘nature and nurture, or ‘gene × environment interactions’. Dynamic gene expression of neuropeptides or their receptors is a key component of signalling in the CNS and their inappropriate regulation is therefore a predicted target underpinning psychiatric disorders and neuropathological processes. Finding the regulatory domains within our genome which have the potential to direct gene expression is a difficult challenge as 98% of our genome is non-coding and, with the exception of proximal promoter regions, such elements can be quite distant from the gene that they regulate. This review will deal with how we can find such domains by addressing both the most conserved non-exonic regions in the genome using comparative genomics and the most recent or constantly evolving DNA such as repetitive DNA or retrotransposons. We shall also explore how polymorphic changes in such domains can be associated with CNS disorders by altering the appropriate gene expression patterns which maintain normal physiology. 相似文献
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Marta I. Sierra Laura Rubio Gustavo F. Bayón Isabel Cobo Pablo Menendez Paula Morales 《Nanotoxicology》2017,11(7):857-870
Humans are increasingly exposed to nanoparticles and, although many of their physiological effects have been described, the molecular mechanisms underlying them are still largely unknown. The present study aimed to determine the possible role of certain epigenetic mechanisms in the cellular response of human lung epithelial cells that are triggered by long-term exposure to titanium dioxide nanoparticles (TiO2NPs) and multi-walled carbon nanotubes (MWCNTs). The results showed that exposure to TiO2NPs had only minor effects on genome-wide DNA methylation. However, we identified 755 CpG sites showing consistent DNA hypomethylation in cells exposed to MWCNTs. These sites were mainly located at low density CpG regions and enhancers, and very frequently on the X chromosome. Our results thus suggest that long-term MWCNT exposure may have important effects on the epigenome. 相似文献
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支气管哮喘是一种复杂的遗传性疾病,受环境因素影响。表观遗传学作为连接遗传易感因素及环境因素的桥梁,在支气管哮喘发病机制中的作用越来越受到人们的重视。DNA 甲基化作为最为常见的表观遗传修饰形式,可受环境及饮食因素的影响,从而对 CD4+T 细胞的分化产生影响,促进哮喘的发生。 相似文献
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Helena Palma-Gudiel Aldo Córdova-Palomera Cristian Tornador Carles Falcón Núria Bargalló Gustavo Deco Lourdes Fañanás 《European neuropsychopharmacology》2018,28(5):579-588
Among the major psychiatric disorders, anxious-depressive disorders stand out as one of the more prevalent and more frequently associated with hypothalamic-pituitary-adrenal (HPA) axis abnormalities. Methylation at the exon 1F of the glucocorticoid receptor gene NR3C1 has been associated with both early stress exposure and risk for developing a psychiatric disorder; however, other NR3C1 promoter regions have been underexplored. Exon 1D emerges as a suggestive new target in stress-related disorders epigenetically sensitive to early adversity. After assessment of 48 monozygotic twin pairs (n=96 subjects) informative for lifetime history of anxious-depressive disorders, they were classified as concordant, discordant or healthy in function of whether both, one or neither twin in each pair had a lifetime diagnosis of anxious-depressive disorders. DNA for epigenetic analysis was extracted from peripheral blood. Exon 1F and exon 1D CpG-specific methylation was analysed by means of pyrosequencing technology. Functional magnetic resonance imaging was available for 54 subjects (n=27 twin pairs). Exon 1D CpG-specific methylation within a glucocorticoid responsive element (GRE) was correlated with familial burden of anxious-depressive disorders (r=0.35, z=2.26, p=0.02). Right hippocampal connectivity was significantly associated with CpG-specific GRE methylation (β=?2.33, t=?2.85, p=0.01). Exon 1F was uniformly hypomethylated across all subgroups of the present sample. GRE hypermethylation at exon 1D of the NR3C1 gene in monozygotic twins concordant for anxious-depressive disorders suggests this region plays a role in increasing vulnerability to psychosocial stress, partly mediated by altered hippocampal connectivity. 相似文献
45.
Iris Šalamon Arčan Katarina Kouter Alja Videtič Paska 《World Journal of Psychiatry》2022,12(9):1150-1168
Depressive disorder is a complex, heterogeneous disease that affects approximately 280 million people worldwide. Environmental, genetic, and neurobiological factors contribute to the depressive state. Since the nervous system is susceptible to shifts in activity of epigenetic modifiers, these allow for significant plasticity and response to rapid changes in the environment. Among the most studied epigenetic modifications in depressive disorder is DNA methylation, with findings centered on the brain-derived neurotrophic factor gene, the glucocorticoid receptor gene, and the serotonin transporter gene. In order to identify biomarkers that would be useful in clinical settings, for diagnosis and for treatment response, further research on antidepressants and alterations they cause in the epigenetic landscape throughout the genome is needed. Studies on cornerstone antidepressants, such as selective serotonin reuptake inhibitors, selective serotonin and norepinephrine reuptake inhibitors, norepinephrine, and dopamine reuptake inhibitors and their effects on depressive disorder are available, but systematic conclusions on their effects are still hard to draw due to the highly heterogeneous nature of the studies. In addition, two novel drugs, ketamine and esketamine, are being investigated particularly in association with treatment of resistant depression, which is one of the hot topics of contemporary research and the field of precision psychiatry. 相似文献
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姜黄素已被证明是一种抗肿瘤药物,它除了对目的蛋白的直接调控外,也可以通过改变表观遗传学作用于目的基因。本文着重对姜黄素所致的DNA去甲基化、组蛋白去乙酰化和miRNA的调节现象以及这些调节对肿瘤的生长影响进行阐述。 相似文献
50.
早期营养不良和成年后代谢性疾病的关系非常密切,且越来越受到关注。研究发现,早期营养不良可通过表观遗传修饰影响肝脏、胰腺、骨骼肌等器官的发育及基因表达水平的改变,从而导致生后以糖代谢紊乱为中心的代谢综合征(metabolicsyndrome,MS)发生。 相似文献