全文获取类型
收费全文 | 353篇 |
免费 | 21篇 |
专业分类
儿科学 | 19篇 |
妇产科学 | 1篇 |
基础医学 | 62篇 |
口腔科学 | 3篇 |
临床医学 | 86篇 |
内科学 | 59篇 |
神经病学 | 19篇 |
特种医学 | 8篇 |
外科学 | 38篇 |
综合类 | 3篇 |
预防医学 | 28篇 |
药学 | 25篇 |
肿瘤学 | 23篇 |
出版年
2023年 | 3篇 |
2021年 | 14篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 10篇 |
2013年 | 16篇 |
2012年 | 24篇 |
2011年 | 23篇 |
2010年 | 22篇 |
2009年 | 18篇 |
2008年 | 16篇 |
2007年 | 20篇 |
2006年 | 20篇 |
2005年 | 18篇 |
2004年 | 20篇 |
2003年 | 12篇 |
2002年 | 21篇 |
2001年 | 16篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 4篇 |
1970年 | 1篇 |
1969年 | 3篇 |
1967年 | 2篇 |
1966年 | 3篇 |
1965年 | 2篇 |
排序方式: 共有374条查询结果,搜索用时 15 毫秒
1.
Xiaoyan Lu Isabelle R. Miousse Sandra V. Pirela Jodene K. Moore Stepan Melnyk 《Nanotoxicology》2016,10(5):629-639
Evidence continues to grow on potential environmental health hazards associated with engineered nanomaterials (ENMs). While the geno- and cytotoxic effects of ENMs have been investigated, their potential to target the epigenome remains largely unknown. The aim of this study is two-fold: 1) determining whether or not industry relevant ENMs can affect the epigenome in vivo and 2) validating a recently developed in vitro epigenetic screening platform for inhaled ENMs. Laser printer-emitted engineered nanoparticles (PEPs) released from nano-enabled toners during consumer use and copper oxide (CuO) were chosen since these particles induced significant epigenetic changes in a recent in vitro companion study. In this study, the epigenetic alterations in lung tissue, alveolar macrophages and peripheral blood from intratracheally instilled mice were evaluated. The methylation of global DNA and transposable elements (TEs), the expression of the DNA methylation machinery and TEs, in addition to general toxicological effects in the lung were assessed. CuO exhibited higher cell-damaging potential to the lung, while PEPs showed a greater ability to target the epigenome. Alterations in the methylation status of global DNA and TEs, and expression of TEs and DNA machinery in mouse lung were observed after exposure to CuO and PEPs. Additionally, epigenetic changes were detected in the peripheral blood after PEPs exposure. Altogether, CuO and PEPs can induce epigenetic alterations in a mouse experimental model, which in turn confirms that the recently developed in vitro epigenetic platform using macrophage and epithelial cell lines can be successfully utilized in the epigenetic screening of ENMs. 相似文献
2.
3.
Fineout-Overholt E Melnyk BM Stillwell SB Williamson KM 《The American journal of nursing》2010,110(11):43-51
This is the seventh article in a series from the Arizona State University College of Nursing and Health Innovation's Center for the Advancement of Evidence-Based Practice. Evidence-based practice (EBP) is a problem-solving approach to the delivery of health care that integrates the best evidence from studies and patient care data with clinician expertise and patient preferences and values. When delivered in a context of caring and in a supportive organizational culture, the highest quality of care and best patient outcomes can be achieved. The purpose of this series is to give nurses the knowledge and skills they need to implement EBP consistently, one step at a time. Articles will appear every two months to allow you time to incorporate information as you work toward implementing EBP at your institution. Also, we've scheduled "Chat with the Authors" calls every few months to provide a direct line to the experts to help you resolve questions. See details below. 相似文献
4.
Ranekka Dean Halia Melnyk Carlita Anglin 《Journal of consumer health on the Internet》2017,21(1):62-70
During recent months, there has been growing international public concern about the Zika virus. As scientific understanding of the Zika virus unfolds, there are still many unanswered questions. Public health officials, clinicians, and consumers alike have questions about the Zika virus and the Zika virus disease. There is a need to know where to turn for the most up-to-date and reliable online information sources. Although aspects of Zika virus disease and associated medical conditions can be frightening, information seekers may find reassurance in the following online sources to guide their understanding of risk, prevention, transmission, affected geographical areas, symptoms, and disease management. 相似文献
5.
Gohla A Klement K Piekorz RP Pexa K vom Dahl S Spicher K Dreval V Häussinger D Birnbaumer L Nürnberg B 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(8):3003-3008
Heterotrimeric G proteins of the G(i) class have been implicated in signaling pathways regulating growth and metabolism under physiological and pathophysiological conditions. Knockout mice carrying inactivating mutations in both of the widely expressed Galpha(i) class genes, Galpha(i2) and Galpha(i3), demonstrate shared as well as gene-specific functions. The presence of a single active allele of Galpha(i3) is sufficient for embryonic development, whereas at least one allele of Galpha(i2) is required for extrauterine life. Mice lacking both Galpha(i2) and Galpha(i3) are massively growth-retarded and die in utero. We have used biochemical and cell biological methods together with in situ liver perfusion experiments to study Galpha(i) isoform-specific functions in Galpha(i2)- and Galpha(i3)-deficient mice. The subcellular localization of Galpha(i3) in isolated mouse hepatocytes depends on the cellular metabolic status. Galpha(i3) localizes to autophagosomes upon starvation-induced autophagy and distributes to the plasma membrane upon insulin stimulation. Analysis of autophagic proteolysis in perfused mouse livers showed that mice lacking Galpha(i3) are deficient in the inhibitory action of insulin. These data indicate that Galpha(i3) is crucial for the antiautophagic action of insulin and suggest an as-yet-unrecognized function for Galpha(i3) on autophagosomal membranes. 相似文献
6.
Kunie Ando Pierre Dourlen Anne-Véronique Sambo Alexis Bretteville Karim Bélarbi Valérie Vingtdeux Sabiha Eddarkaoui Hervé Drobecq Antoine Ghestem Séverine Bégard Emmanuelle Demey-Thomas Patricia Melnyk Caroline Smet Guy Lippens Claude-Alain Maurage Marie-Laure Caillet-Boudin Yann Verdier Joelle Vinh Isabelle Landrieu Marie-Christine Galas David Blum Malika Hamdane Nicolas Sergeant Luc Buée 《Neurobiology of aging》2013
A prerequisite to dephosphorylation at Ser–Pro or Thr–Pro motifs is the isomerization of the imidic peptide bond preceding the proline. The peptidyl-prolyl cis/trans isomerase named Pin1 catalyzes this mechanism. Through isomerization, Pin1 regulates the function of a growing number of targets including the microtubule-associated tau protein and is supposed to be deregulated Alzheimer's disease (AD). Using proteomics, we showed that Pin1 is posttranslationally modified on more than 5 residues, comprising phosphorylation, N-acetylation, and oxidation. Although Pin1 expression remained constant, Pin1 posttranslational two-dimensional pattern was modified by tau overexpression in a tau-inducible neuroblastoma cell line, in our THY-Tau22 mouse model of tauopathy as well as in AD. Interestingly, in all of these systems, Pin1 modifications were very similar. In AD brain tissue when compared with control, Pin1 is hyperphosphorylated at serine 16 and found in the most insoluble hyperphosphorylated tau fraction of AD brain tissue. Furthermore, in all tau pathology conditions, acetylation of Pin1 may also contribute to the differences observed. In conclusion, Pin1 displays several posttranslational modifications, which are specific in tauopathies and may be useful as biomarker. 相似文献
7.
8.
Vladyslav Nikolayevskyy Yanina Balabanova Tatyana Simak Nadezhda Malomanova Ivan Fedorin Francis Drobniewski 《BMC clinical pathology》2009,9(1):2
Background
Russia is a high tuberculosis (TB) burden country with a high prevalence of multidrug resistant tuberculosis (MDRTB). Molecular assays for detection of MDRTB on clinical specimens are not widely available in Russia. 相似文献9.
Cobalamin deficiency with and without neurologic abnormalities: differences in homocysteine and methionine metabolism 总被引:3,自引:0,他引:3 下载免费PDF全文
The unknown biochemical basis for neurologic dysfunction in cobalamin deficiency and the frequent divergence between neurologic and hematologic manifestations led us to study homocysteine metabolism in 22 patients with pernicious anemia. Serum levels of total homocysteine (tHcy), methionine, S-adenosylmethionine (AdoMet), cysteine, cysteinylglycine (cys-gly), and glutathione (GSH) were measured. Only levels of tHcy and cysteine were increased and only GSH was decreased in cobalamin deficiency as a whole, compared with 17 control subjects. AdoMet correlated only with methionine levels (P =.015) and cysteine only with cys-gly (P =.007) in healthy subjects, but in cobalamin-deficient patients AdoMet correlated instead with cysteine, cys-gly, and folate levels only (P =.008, P =.03, and P =.03, respectively). Significant differences appeared in clinically subgrouped cobalamin-deficient patients. The 11 patients with neurologic defects had higher mean levels of folate (27.9 versus 15.4 nM), AdoMet (117.2 versus 78.6 nM), cysteine (462 versus 325 microM), and cys-gly (85.0 versus 54.7 microM) than the 11 neurologically unaffected patients. Cobalamin therapy restored all metabolic changes to normal. The results indicate that changes in several metabolic pathways differ in patients with and without neurologic dysfunction. Cysteine levels were the most significant predictors of neurologic dysfunction, but it is unclear if they are direct or indirect indicators of neurotoxicity. The higher AdoMet levels in neurologically affected patients may result from inhibition of glycine N-methyltransferase by those patients' higher folate levels. The origin of the folate differences is unclear and possibly varied. Low AdoMet and GSH levels were independent predictors of anemia. 相似文献
10.