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排序方式: 共有721条查询结果,搜索用时 15 毫秒
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Costan Victor Vlad Ciocan-Pendefunda Constantin-Catalin Ciofu Mihai Liviu Boisteanu Otilia Timofte Daniel Vasile Gheorghe Liliana Bogdanici Camelia Preda Cristina 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2020,258(10):2313-2320
Graefe's Archive for Clinical and Experimental Ophthalmology - The purpose of this study is to share our experience on the use of different orbital decompression techniques, as well as the... 相似文献
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McQueen AP Zhang D Hu P Swenson L Yang Y Zaha VG Hoffman JL Yun UJ Chakrabarti G Wang Z Albertine KH Abel ED Litwin SE 《Journal of molecular and cellular cardiology》2005,39(6):882-892
Diabetics have worse outcomes than nondiabetics after a variety of cardiac insults. We tested the hypothesis that impaired insulin receptor signaling in myocytes worsens cardiac remodeling and function following injury, even in the absence of hyperglycemia. Mice with cardiomyocyte-restricted knock out of the insulin receptor (CIRKO) and wild type (WT) mice were treated with isoproterenol (ISO) for 2 or 5 days. Heart rates and cardiac mass increased comparably following ISO in WT and CIRKO mice. After 5 days, WT hearts were hyperdynamic by echocardiographic and left ventricular pressure measurements. However, CIRKO hearts had a blunted increase in contractility and relaxation following ISO. Interestingly, single myocytes isolated from both CIRKO ISO and WT ISO hearts had increased cellular shortening with prolonged time to peak shortening vs. respective shams. Thus, loss of myocytes or extramyocyte factors, rather than intrinsic dysfunction of surviving myocytes, caused the blunted inotropic response in ISO treated CIRKO hearts. Indeed, CIRKO ISO mice had increased troponin release after 2 days and greater interstitial and sub-endocardial fibrosis at 5 days than did ISO WT. Apoptosis assessed by TUNEL and caspase staining was increased in CIRKO ISO compared to WT ISO hearts; however, very few of the apoptotic nuclei were clearly in cardiac myocytes. After 5 days of ISO treatment, VEGF expression was increased in WT but not in CIRKO hearts. In keeping with this finding, capillary density was reduced in CIRKO ISO relative to WT ISO. Basal expression of hypoxia-inducible factor-1alpha was lower in CIRKO vs. WT hearts and may explain the blunted VEGF response. Thus, absence of insulin receptor signaling in the cardiac myocyte worsens catecholamine-mediated myocardial injury, at least in part, via mechanisms that tend to impair myocardial blood flow and increase ischemic injury. 相似文献
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T. Jake Samuel Rhys Beaudry Satyam Sarma Vlad Zaha Mark J. Haykowsky Michael D. Nelson 《Current heart failure reports》2018,15(6):332-339
Purpose of Review
This review summarizes recent developments highlighting the clinical utility of diastolic stress testing along the heart failure continuum.Recent Findings
Invasive hemodynamic assessment of cardiac filling pressures during physiological stress is the gold-standard technique for unmasking diastolic dysfunction. Non-invasive surrogate techniques, such as Doppler ultrasound, have shown excellent agreement with invasive approaches and are now recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. While cycle exercise is often advocated, recent evidence supports the use of isometric handgrip as a viable alternative stressor.Summary
Diastolic stress testing is a powerful tool to enhance detection of diastolic dysfunction, is able to differentiate between cardiac and non-cardiac pathology, and should be incorporated into routine clinical assessment.16.
Can F. Koyuncu Cheng Lu Kaustav Bera Zelin Zhang Jun Xu Paula Toro German Corredor Deborah Chute Pingfu Fu Wade L. Thorstad Farhoud Faraji Justin A. Bishop Mitra Mehrad Patricia D. Castro Andrew G. Sikora Lester D.R. Thompson R.D. Chernock Krystle A. Lang Kuhs Jingqin Luo Vlad Sandulache David J. Adelstein Shlomo Koyfman James S. Lewis Jr. Anant Madabhushi 《The Journal of clinical investigation》2021,131(8)
BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning–based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis–free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37–2.30), 1.94 (1.44–2.60), and 1.88 (1.43–2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain–based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government. 相似文献
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Zobair Younossi Maria Stepanova Arun J. Sanyal Stephen A. Harrison Vlad Ratziu Manal F. Abdelmalek Anna Mae Diehl Stephen Caldwell Mitchell L. Shiffman Raul Aguilar Schall Bryan McColgan G. Mani Subramanian Robert P. Myers Andrew Muir Nezam H. Afdhal Jaime Bosch Zachary Goodman 《Journal of hepatology》2018,68(6):1365-1370
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Ovidiu Chioncel John Parissis Alexandre Mebazaa Holger Thiele Steffen Desch Johann Bauersachs Veli‐Pekka Harjola Elena‐Laura Antohi Mattia Arrigo Tuvia B. Gal Jelena Celutkiene Sean P. Collins Daniel DeBacker Vlad A. Iliescu Ewa Jankowska Tiny Jaarsma Kalliopi Keramida Mitja Lainscak Lars H Lund Alexander R. Lyon Josep Masip Marco Metra Oscar Miro Andrea Mortara Christian Mueller Wilfried Mullens Maria Nikolaou Massimo Piepoli Susana Price Giuseppe Rosano Antoine Vieillard‐Baron Jean M. Weinstein Stefan D. Anker Gerasimos Filippatos Frank Ruschitzka Andrew J.S. Coats Petar Seferovic 《European journal of heart failure》2020,22(8):1315-1341
Cardiogenic shock (CS) is a complex multifactorial clinical syndrome with extremely high mortality, developing as a continuum, and progressing from the initial insult (underlying cause) to the subsequent occurrence of organ failure and death. There is a large spectrum of CS presentations resulting from the interaction between an acute cardiac insult and a patient's underlying cardiac and overall medical condition. Phenotyping patients with CS may have clinical impact on management because classification would support initiation of appropriate therapies. CS management should consider appropriate organization of the health care services, and therapies must be given to the appropriately selected patients, in a timely manner, whilst avoiding iatrogenic harm. Although several consensus‐driven algorithms have been proposed, CS management remains challenging and substantial investments in research and development have not yielded proof of efficacy and safety for most of the therapies tested, and outcome in this condition remains poor. Future studies should consider the identification of the new pathophysiological targets, and high‐quality translational research should facilitate incorporation of more targeted interventions in clinical research protocols, aimed to improve individual patient outcomes. Designing outcome clinical trials in CS remains particularly challenging in this critical and very costly scenario in cardiology, but information from these trials is imperiously needed to better inform the guidelines and clinical practice. The goal of this review is to summarize the current knowledge concerning the definition, epidemiology, underlying causes, pathophysiology and management of CS based on important lessons from clinical trials and registries, with a focus on improving in‐hospital management. 相似文献
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Rahul A. Parikh Leonard J. Appleman Julie E. Bauman Madhav Sankunny Dale W. Lewis Anda Vlad Susanne M. Gollin 《Genes, chromosomes & cancer》2014,53(1):25-37
The ATR‐CHEK1 pathway is upregulated and overactivated in Ataxia Telangiectasia (AT) cells, which lack functional ATM protein. Loss of ATM in AT confers radiosensitivity, although ATR‐CHEK1 pathway overactivation compensates, leads to prolonged G2 arrest after treatment with ionizing radiation (IR), and partially reverses the radiosensitivity. We observed similar upregulation of the ATR–CHEK1 pathway in a subset of oral squamous cell carcinoma (OSCC) cell lines with ATM loss. In the present study, we report copy number gain, amplification, or translocation of the ATR gene in 8 of 20 OSCC cell lines by FISH; whereas the CHEK1 gene showed copy number loss in 12 of 20 cell lines by FISH. Quantitative PCR showed overexpression of both ATR and CHEK1 in 7 of 11 representative OSCC cell lines. Inhibition of ATR or CHEK1 with their respective siRNAs resulted in increased sensitivity of OSCC cell lines to IR by the colony survival assay. siRNA‐mediated ATR or CHEK1 knockdown led to loss of G2 cell cycle accumulation and an increased sub‐G0 apoptotic cell population by flow cytometric analysis. In conclusion, the ATR‐CHEK1 pathway is upregulated in a subset of OSCC with distal 11q loss and loss of the G1 phase cell cycle checkpoint. The upregulated ATR‐CHEK1 pathway appears to protect OSCC cells from mitotic catastrophe by enhancing the G2 checkpoint. Knockdown of ATR and/or CHEK1 increases the sensitivity of OSCC cells to IR. These findings suggest that inhibition of the upregulated ATR–CHEK1 pathway may enhance the efficacy of ionizing radiation treatment of OSCC. © 2013 Wiley Periodicals, Inc. 相似文献
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