全文获取类型
收费全文 | 237篇 |
免费 | 14篇 |
国内免费 | 4篇 |
专业分类
儿科学 | 5篇 |
妇产科学 | 10篇 |
基础医学 | 21篇 |
临床医学 | 26篇 |
内科学 | 59篇 |
皮肤病学 | 2篇 |
神经病学 | 14篇 |
特种医学 | 8篇 |
外科学 | 26篇 |
综合类 | 8篇 |
预防医学 | 43篇 |
眼科学 | 2篇 |
药学 | 18篇 |
肿瘤学 | 13篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 2篇 |
2017年 | 6篇 |
2016年 | 6篇 |
2015年 | 5篇 |
2014年 | 19篇 |
2013年 | 9篇 |
2012年 | 23篇 |
2011年 | 20篇 |
2010年 | 17篇 |
2009年 | 9篇 |
2008年 | 13篇 |
2007年 | 19篇 |
2006年 | 10篇 |
2005年 | 14篇 |
2004年 | 18篇 |
2003年 | 13篇 |
2002年 | 13篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1962年 | 1篇 |
排序方式: 共有255条查询结果,搜索用时 15 毫秒
1.
2.
Waller SA Armstrong KJ McGrath AM Sullivan CL 《Journal of autism and developmental disorders》1999,29(6):485-490
This review summarizes subject selection and diagnostic procedures documented in the Journal of Autism and Developmental Disorders. One hundred forty-two empirical articles published between February 1993 and April 1997 were examined. Reviewers independently evaluated articles using a coding instrument developed by the authors. Results indicated that a majority of researchers reported the use of one or more standard diagnostic criteria in classifying their subjects. However, numerous studies did not report the methods by which the diagnostic criteria were quantified or applied. Additionally, there was a lack of clear specification of inclusion and exclusion criteria for comorbid disorders. Improving the documentation of diagnostic practices in research on autism will benefit researchers and practitioners. 相似文献
3.
Emily N. Dunn Teresa M. Ferrara-Bowens Mark E. Chachich Cary L. Honnold Cristin C. Rothwell Heidi M. Hoard-Fruchey 《Toxicology mechanisms and methods》2018,28(8):563-572
Mice and other rodents are typically utilized for chemical warfare nerve agent research. Rodents have large amounts of carboxylesterase in their blood, while humans do not. Carboxylesterase nonspecifically binds to and detoxifies nerve agent. The presence of this natural bioscavenger makes mice and other rodents poor models for studies identifying therapeutics to treat humans exposed to nerve agents. To obviate this problem, a serum carboxylesterase knockout (Es1 KO) mouse was created. In this study, Es1 KO and wild type (WT) mice were assessed for differences in gene expression, nerve agent (soman; GD) median lethal dose (MLD) values, and behavior prior to and following nerve agent exposure. No expression differences were detected between Es1 KO and WT mice in more than 34?000 mouse genes tested. There was a significant difference between Es1 KO and WT mice in MLD values, as the MLD for GD-exposed WT mice was significantly higher than the MLD for GD-exposed Es1 KO mice. Behavioral assessments of Es1 KO and WT mice included an open field test, a zero maze, a Barnes maze, and a sucrose preference test (SPT). While sex differences were observed in various measures of these tests, overall, Es1 KO mice behaved similarly to WT mice. The two genotypes also showed virtually identical neuropathological changes following GD exposure. Es1 KO mice appear to have an enhanced susceptibility to GD toxicity while retaining all other behavioral and physiological responses to this nerve agent, making the Es1 KO mouse a more human-like model for nerve agent research. 相似文献
4.
K. Vecchiato A. Egloff O. Carney A. Siddiqui E. Hughes L. Dillon K. Colford E. Green R.P.A.G. Texeira A.N. Price G. Ferrazzi J.V. Hajnal D.W. Carmichael L. Cordero-Grande J. OMuircheartaigh 《AJNR. American journal of neuroradiology》2021,42(4):774
BACKGROUND AND PURPOSE:Head motion causes image degradation in brain MR imaging examinations, negatively impacting image quality, especially in pediatric populations. Here, we used a retrospective motion correction technique in children and assessed image quality improvement for 3D MR imaging acquisitions.MATERIALS AND METHODS:We prospectively acquired brain MR imaging at 3T using 3D sequences, T1-weighted MPRAGE, T2-weighted TSE, and FLAIR in 32 unsedated children, including 7 with epilepsy (age range, 2–18 years). We implemented a novel motion correction technique through a modification of k-space data acquisition: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). For each participant and technique, we obtained 3 reconstructions as acquired (Aq), after DISORDER motion correction (Di), and Di with additional outlier rejection (DiOut). We analyzed 288 images quantitatively, measuring 2 objective no-reference image quality metrics: gradient entropy (GE) and MPRAGE white matter (WM) homogeneity. As a qualitative metric, we presented blinded and randomized images to 2 expert neuroradiologists who scored them for clinical readability.RESULTS:Both image quality metrics improved after motion correction for all modalities, and improvement correlated with the amount of intrascan motion. Neuroradiologists also considered the motion corrected images as of higher quality (Wilcoxon z = −3.164 for MPRAGE; z = −2.066 for TSE; z = −2.645 for FLAIR; all P < .05).CONCLUSIONS:Retrospective image motion correction with DISORDER increased image quality both from an objective and qualitative perspective. In 75% of sessions, at least 1 sequence was improved by this approach, indicating the benefit of this technique in unsedated children for both clinical and research environments.Head motion is a common cause of image degradation in brain MR imaging. Motion artifacts negatively impact MR image quality and therefore radiologists’ capacity to read the images, ultimately affecting patient clinical care.1 Motion artifacts are more common in noncompliant patients,2 but even in compliant adults, intrascan movement is reported in at least 10% of cases.3 For children who require high-resolution MR images, obtaining optimal image quality can be challenging, owing to the requirement to stay still over long durations needed for acquisition.4 Sedation can be an option, but it carries higher risks, costs, and preparation and recovery time.5In conditions such as intractable focal epilepsy, identification of an epileptogenic lesion is clinically important to guide surgical treatment. However, these lesions can be visually subtle, particularly in children in whom subtle cortical dysplasias are more common.6 Dedicated epilepsy MR imaging protocols use high-resolution 3D sequences to allow better cortical definition and free reformatting of orientation but involve acquisition times in the order of minutes, so data collection becomes more sensitive to motion.7For children in particular, multiple strategies are available for minimizing motion during MR examinations. Collaboration with play specialists using mock scanners and training or projecting a cartoon are good approaches to reduce anxiety.8,9 These tools are not always available in clinical radiology and, even with these strategies, motion can still be an issue.10 Different scanning approaches to correct for intrascan motion have been proposed. Broadly, prospective methods track head motion in real time and modify the acquisition directions accordingly.11 These approaches are applicable to a wide range of sequences but require optical systems with external tracking markers, sometimes uncomfortable or impractical, and extra setup can ultimately result in longer examinations. Furthermore, these approaches may also not be robust to continuous motion.11-13 Retrospective techniques have also been proposed, in some cases relying on imaging navigators that are not compatible with all standard sequences or contrasts.12Here, we use a more general retrospective motion correction technique: Distributed and Incoherent Sample Orders for Reconstruction Deblurring by using Encoding Redundancy (DISORDER). In this method, k-space samples are reordered to enable retrospective motion correction during image reconstruction.14 Our hypothesis is that DISORDER improves clinical MR imaging quality and readability. To assess its use for clinical sequences, we acquired a dedicated epilepsy MR imaging protocol in 32 children across a wide age range. We used both objective image quality metrics and expert neuroradiologist ratings to evaluate the outcome after motion correction. 相似文献
5.
Shane Cullinan Aoife Fleming Denis O'Mahony Cristin Ryan David O'Sullivan Paul Gallagher Stephen Byrne 《British journal of clinical pharmacology》2015,79(5):860-869
Aims
Older patients commonly suffer from multimorbidites and take multiple medications. As a result, these patients are more vulnerable to potentially inappropriate prescribing (PIP). PIP in older patients may result in adverse drug events (ADEs) and hospitalizations. However, little has been done to identify why PIP occurs. The objectives of this study were (i) to identify hospital doctors'' perceptions as to why PIP occurs, (ii) to identify the barriers to addressing the issues identified and (iii) to determine which intervention types would be best suited to improving prescribing.Methods
Semi-structured interviews based on the Theoretical Domains Framework (TDF), a tool used to apply behaviour change theories, were conducted with 22 hospital doctors. Content analysis was conducted to identify domains of the TDF that could be targeted to improve prescribing for older people. These domains were then mapped to the behaviour change wheel to identify possible intervention types.Results
Content analysis identified five of the 12 domains in the TDF as relevant: (i) environmental context and resources, (ii) knowledge, (iii) skills, (iv) social influences and (v) memory/attention and decision processes. Using the behaviour change wheel, the types of interventions deemed suitable were those based on training and environmental restructuring.Conclusion
This study shows that doctors feel there is insufficient emphasis on geriatric pharmacotherapy in their undergraduate/postgraduate training. An intervention providing supplementary training, with particular emphasis on decision processes and dealing with social influences would be justified. This study has, however, uncovered many areas for potential intervention in the future. 相似文献6.
Litten RZ Fertig JB Falk DE Ryan ML Mattson ME Collins JF Murtaugh C Ciraulo D Green AI Johnson B Pettinati H Swift R Afshar M Brunette MF Tiouririne NA Kampman K Stout R;NCIG Study Group 《Alcoholism, clinical and experimental research》2012,36(3):406-416
Background: Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol‐dependent population of very heavy drinkers. Methods: In this double‐blind, placebo‐controlled trial, 224 alcohol‐dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization. Results: No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy‐drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%). Conclusions: This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy‐drinking alcohol‐dependent patients. 相似文献
7.
Thomas F. Schultz Cristin Keelin Fitzpatrick D. Wilson Freshwater James A. Morris Jr. 《Conservation Genetics Resources》2013,5(3):599-601
Lionfish (Pterois volitans and Pterois miles) are the first non-native marine reef fish to become established in the Western North Atlantic and Caribbean Sea. Next-generation sequencing techniques were employed to identify 18 polymorphic microsatellite loci for P. volitans and P. miles from waters off North Carolina, USA. Allele frequencies for all 18 loci conformed to Hardy–Weinberg expectations after correction for multiple comparisons, the number of alleles ranged from 2 to 20 (mean = 7.1), and observed heterozygosities ranged from 0.200 to 0.938 (mean Ho = 0.636). All 18 loci cross-amplified DNAs from representative haplotypes of both P. volitans and P. miles, and the vast majority of alleles were shared. These are the first highly polymorphic nuclear markers described for invasive lionfish and will be useful for characterizing population connectivity and monitoring the progress of the invasion on reef habitats of the Western Atlantic. 相似文献
8.
9.
Francis W. Hunter Jagdish K. Jaiswal Daniel G. Hurley H.D. Sarath Liyanage Sarah P. McManaway Yongchuan Gu Susan Richter Jingli Wang Moana Tercel Cristin G. Print William R. Wilson Frederik B. Pruijn 《Biochemical pharmacology》2014
The nitro-chloromethylbenzindoline prodrug SN29428 has been rationally designed to target tumour hypoxia. SN29428 is metabolised to a DNA minor groove alkylator via oxygen-sensitive reductive activation initiated by unknown one-electron reductases. The present study sought to identify reductases capable of activating SN29428 in tumours. Expression of candidate reductases in cell lines was modulated using forced expression and, for P450 (cytochrome) oxidoreductase (POR), by zinc finger nuclease-mediated gene knockout. Affymetrix microarray mRNA expression of flavoreductases was correlated with SN29428 activation in a panel of 23 cancer cell lines. Reductive activation and cytotoxicity of prodrugs were measured using mass spectrometry and antiproliferative assays, respectively. SN29428 activation under hypoxia was strongly attenuated by the pan-flavoprotein inhibitor diphenyliodonium, but less so by knockout of POR suggesting other flavoreductases contribute. Forced expression of 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), as well as POR, increased activation of SN29428 in hypoxic HCT 116 cells. SN29428 activation strongly correlated with expression of POR and also FAD-dependent oxidoreductase domain containing 2 (FOXRED2), in cancer cell lines. This association persisted after removing the effect of POR enzyme activity using first-order partial correlation. Forced expression of FOXRED2 increased SN29428 activation and cytotoxicity in hypoxic HEK293 cells and also increased activation of hypoxia-targeted prodrugs PR-104A, tirapazamine and SN30000, and increased cytotoxicity of the clinical-stage prodrug TH-302. Thus this study has identified three flavoreductases capable of enzymatically activating SN29428, one of which (FOXRED2) has not previously been implicated in xenobiotic metabolism. These results will inform future development of biomarkers predictive of SN29428 sensitivity. 相似文献
10.