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41.
Jacob Matthew Eckstein Nicole Nolan Erin Healy Chadwick Lewis Wright Angita Jain Christian Louis Barney Iman Washington Joseph Paul McElroy John Christopher Grecula Jessica Lynn Wobb Darrion Luther Mitchell Eric Miller Mauricio Gamez Dukagjin Blakaj Virginia Diavolitsis Aashish Bhatt 《Head & neck》2020,42(9):2405-2413
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Lu Victor M. O’Connor Kyle P. Shah Ashish H. Eichberg Daniel G. Luther Evan M. Komotar Ricardo J. Ivan Michael E. 《Journal of neuro-oncology》2020,148(2):221-229
Journal of Neuro-Oncology - The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular... 相似文献
44.
目的对自闭症病人给予被动性语言刺激,评价采用功能性磁共振(MR)成像作为判断病人有无语言缺陷的客观指标的可行性。材料与方法本研究为前瞻性研究,研究方 相似文献
45.
Andr M. Ribeiro-dos-Santos Megan S. Hogan Raven D. Luther Ran Brosh Matthew T. Maurano 《Genome research》2022,32(3):425
The specificity of interactions between genomic regulatory elements and potential target genes is influenced by the binding of insulator proteins such as CTCF, which can act as potent enhancer blockers when interposed between an enhancer and a promoter in a reporter assay. But not all CTCF sites genome-wide function as insulator elements, depending on cellular and genomic context. To dissect the influence of genomic context on enhancer blocker activity, we integrated reporter constructs with promoter-only, promoter and enhancer, and enhancer blocker configurations at hundreds of thousands of genomic sites using the Sleeping Beauty transposase. Deconvolution of reporter activity by genomic position reveals distinct expression patterns subject to genomic context, including a compartment of enhancer blocker reporter integrations with robust expression. The high density of integration sites permits quantitative delineation of characteristic genomic context sensitivity profiles and their decomposition into sensitivity to both local and distant DNase I hypersensitive sites. Furthermore, using a single-cell expression approach to test the effect of integrated reporters for differential expression of nearby endogenous genes reveals that CTCF insulator elements do not completely abrogate reporter effects on endogenous gene expression. Collectively, our results lend new insight into genomic regulatory compartmentalization and its influence on the determinants of promoter–enhancer specificity.A boundary model offers an attractive paradigm for understanding regulatory specificity in mammalian genomes through the delineation of independent regulatory domains. Insulators are a class of genomic regulatory elements that block interaction of enhancers with their cognate promoters (Phillips and Corces 2009). Enhancer blocker activity is canonically defined by a reporter assay that interposes a candidate insulator element between a weak promoter and an enhancer (Chung et al. 1993), while barrier insulators protect transgenes from silencing owing to spreading of heterochromatin (West et al. 2002). Insulators have also been used to counter genotoxicity from transgene enhancer activation of endogenous oncogenes (Li et al. 2009; Liu et al. 2015). Known insulators such as the chicken beta-globin hypersensitive site 4 element or the Igf2/H19 imprinting control region (Bell and Felsenfeld 2000) are composite elements with enhancer blocker, barrier, and other activities (Dickson et al. 2010), and often have secondary functions, such as silencers (Qi et al. 2015).The architectural protein CTCF is the only known vertebrate insulator protein, and its binding can confer a potent enhancer blocking effect (Phillips and Corces 2009). Additionally, binding sites for CTCF colocalize with genomic features such as topologically associated domain boundaries (Dixon et al. 2012), but direct functional analysis of these sites is impeded by the difficulty of genome engineering at the relevant scales. Although binding affinity, DNA methylation, and recognition sequence orientation appear to confer some specificity for CTCF sites involved in domain organization (de Wit et al. 2015; Guo et al. 2015; Sanborn et al. 2015), these factors alone remain inadequate to distinguish true insulator elements impacting expression of nearby genes from the ∼100,000 CTCF sites genome-wide (Maurano et al. 2015; Tycko et al. 2019). Stably integrated reporter assays have shed light on the mechanics of insulator function, but such methods do not assess interaction with the surrounding endogenous genomic elements (Walters et al. 1999). In contrast, integrated barcoded reporter assays (Akhtar et al. 2013; Maricque et al. 2019; Moudgil et al. 2020) offer the potential to directly assess the interaction between novel CTCF sites and the endogenous genomic landscape.Here, we aim to functionally characterize endogenous genomic regulatory elements through their effect on integrated reporters. We describe a high-throughput randomly integrated barcoded reporter platform based on a previously described enhancer blocker construct interposing a potent CTCF insulator element (Liu et al. 2015) between a weak promoter and a potent enhancer. We integrate these reporters, both with and without insulator elements, randomly throughout the genome of K562 erythroleukemia cells using the Sleeping Beauty transposase system. We use the unique reporter barcodes to map individual insertion locations and enable position-specific readout of genomic context effects. Finally, we apply single-cell RNA-seq (scRNA-seq) to detect specific reporter integrations that perturb endogenous gene expression. 相似文献
46.
Rosson GD Holton LH Silverman RP Singh NK Nahabedian MY 《Journal of reconstructive microsurgery》2005,21(4):239-242
Microsurgeons currently employ the internal mammary artery and vein as recipient vessels for microvascular reconstruction of the breast with increasing frequency. Recent reports have demonstrated that the perforating branches of the internal mammary artery and vein can also be used as recipient vessels. The purpose of the following cadaver study was to determine the location and diameter of these internal mammary perforators and whether they are suitable as recipient vessels. Ten fresh cadavers were obtained for this project. Using a micrometer under loupe magnification, bilateral measurements were taken of the perforators from the first five interspaces. The largest arterial perforator averaged 1.74 mm in diameter and the largest venous perforator averaged 1.78 mm in diameter. The largest perforators were most commonly found in the second interspace. Based on the results of this study, the internal mammary perforators appear to have suitable diameter for microvascular anastomosis and should be considered. 相似文献
47.
Abstract A comprehensive understanding of language organization in the brain, it is argued, necessitates additional research on both language-particular characteristics and the issue of bilingualism. An analysis of current research on aphasia in bilinguals and American Sign Language (ASL) signers is presented. Central to the presentation is the need for future research to be conducted within the framework advocated. 相似文献
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49.
Luther G. Kalb J. K. Law Rebecca Landa Paul A. Law 《Journal of autism and developmental disorders》2010,40(11):1389-1402
The present study investigated differences among children with three different patterns of autism symptom onset: regression,
plateau, and no loss and no plateau. Cross-sectional data were collected from parents of children aged 3–17 years with an
autism spectrum disorder (n = 2,720) who were recruited through a US-based online research database. Parental report of developmental characteristics
was assessed through a parent questionnaire, and current autism symptoms were measured via the Social Responsiveness Scale
and Social Communication Questionnaire. Multivariate analyses indicated that children with regression had a distinct developmental
pattern marked by less delayed early development. However, following regression, these children evinced elevated autism symptom
scores and an increased risk for poorer outcomes when compared with the other onset groups. 相似文献
50.
Antibiotics are associated with lower relapse rates in outpatients with acute exacerbations of COPD 总被引:8,自引:0,他引:8
BACKGROUND: COPD is a complex disease with exacerbations characterized by worsening of symptoms resulting in deteriorating lung function. STUDY OBJECTIVE: To assess predictive factors of relapse for patients with acute exacerbations of COPD (AECB). DESIGN: Retrospective cohort analysis of visits for AECB. SETTING: Veterans Affairs Medical Center. PATIENTS: Three hundred sixty-two visits (173 patients) with documented COPD treated as outpatients for AECB. MEASUREMENTS: Severity of underlying COPD, severity of AECB, comorbid conditions, therapy, and relapse rates (return visit within 14 days with persistent or worsening symptoms). RESULTS: Each visit was analyzed individually (referred to as a patient-visit). One group received antibiotics (270 patient-visits), and the second group (92 patient-visits) did not. Both groups had similar demographics and severity of underlying COPD. The overall relapse rate was 22%. The majority of patient-visits (95%) with severe symptoms at presentation were prescribed antibiotics vs only 40% of those with mild symptoms. Twenty-nine of 92 patient-visits (32%) were followed by relapse in the group that was not given antibiotics, whereas only 50 of 270 (19%) treated with antibiotics relapsed (p < 0.001). Those treated with amoxicillin had an even higher relapse rate (20 of 37 patient-visits, or 54%) than those who did not receive antibiotics (p = 0.006). CONCLUSIONS: Relapse from AECB was not related to the severity of underlying disease or to the severity of the acute exacerbation. Patients treated with antibiotics had significantly lower relapse rates than those who did not receive antibiotics. However, the specific choice of antibiotic is important because those treated with amoxicillin had the highest relapse rates of all groups. 相似文献