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31.
Brandon P. Verdoorn MD Tamara K. Evans BS Gregory J. Hanson MD Yi Zhu PhD Larissa G. P. Langhi Prata PhD Robert J. Pignolo MD PhD Elizabeth J. Atkinson MS Erin O. Wissler-Gerdes MA George A. Kuchel MD Joan B. Mannick MD Stephen B. Kritchevsky PhD Sundeep Khosla MD Stacey A. Rizza MD Jeremy D. Walston MD Nicolas Musi MD Lewis A. Lipsitz MD Douglas P. Kiel MD Raymond Yung MB ChB Nathan K. LeBrasseur PhD Ravinder J. Singh PhD Teresa McCarthy MD MS Michael A. Puskarich MD Laura J. Niedernhofer MD PhD Paul D. Robbins PhD Matthew Sorenson JD MA Tamara Tchkonia PhD James L. Kirkland MD PhD 《Journal of the American Geriatrics Society》2021,69(11):3023-3033
The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials. 相似文献
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Chunri Yan Ye-Hwan Kim Ho Won Kang Sung Phil Seo Pildu Jeong Il-Seok Lee Dongho Kim Jung Min Kim Yung Hyun Choi Sung-Kwon Moon Seok Joong Yun Wun-Jae Kim 《Journal of Korean medical science》2015,30(12):1784-1792
The potential use of urinary nucleic acids as diagnostic markers in prostate cancer (PCa) was evaluated. Ninety-five urine samples and 234 prostate tissue samples from patients with PCa and benign prostatic hyperplasia (BPH) were analyzed. Micro-array analysis was used to identify candidate genes, which were verified by the two-gene expression ratio and validated in tissue mRNA and urinary nucleic acid cohorts. Real-time quantitative polymerase chain reaction (qPCR) was used to measure urinary nucleic acid levels and tissue mRNA expression. The TSPAN13-to-S100A9 ratio was selected to determine the diagnostic value of urinary nucleic acids in PCa (P = 0.037) and shown to be significantly higher in PCa than in BPH in the mRNA and nucleic acid cohort analyses (P < 0.001 and P = 0.013, respectively). Receiver operating characteristic (ROC) analysis showed that the area under the ROC curve was 0.898 and 0.676 in tissue mRNA cohort and urinary nucleic acid cohort, respectively. The TSPAN13-to-S100A9 ratio showed a strong potential as a diagnostic marker for PCa. The present results suggest that the analysis of urine supernatant can be used as a simple diagnostic method for PCa that can be adapted to the clinical setting in the future. 相似文献
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Mary E. Matsumoto Jessica Berry Herbie Yung Martha Matsumoto Michael C. Munin 《PM & R》2018,10(4):357-364
Background
Ultrasound guidance is increasingly being used for neurolytic procedures that have traditionally been done with electrical stimulation (e-stim) guidance alone. Ultrasound visualization with e-stim?guided neurolysis can potentially allow adjustments in injection protocols that will reduce the volume of neurolytic agent needed to achieve clinical improvement.Objective
This study compared e-stim only to e-stim with ultrasound guidance in phenol neurolysis of the musculocutaneous nerve (MCN) for elbow flexor spasticity. We also evaluated the ultrasound appearance of the MCN in this population.Design
Retrospective review.Setting
University hospital outpatient clinic.Participants
Adults (N = 167) receiving phenol neurolysis to the MCN for treatment of elbow flexor spasticity between 1997 and 2014 and adult control subjects.Methods
For each phenol injection of the MCN, the method of guidance, volume of phenol injected, technical success, improved range of motion at the elbow postinjection, adverse effects, reason for termination of injections, and details of concomitant botulinum toxin injection were recorded. The ultrasound appearance of the MCN, including nerve cross-sectional area and shape, were recorded and compared between groups.Main Outcome Measures
The volume of phenol injected and MCN cross-sectional area and shape as demonstrated by ultrasound.Results
The addition of ultrasound to e-stim?guided phenol neurolysis was associated with lower doses of phenol when compared to e-stim guidance alone (2.31 mL versus 3.69 mL, P < .001). With subsequent injections, the dose of phenol increased with e-stim guidance (P < .001), but not with e-stim and ultrasound guidance (P = .95). Both methods of guidance had high technical success, improved ROM at elbow postinjection, and low rates of adverse events. In comparing the ultrasound appearance of the MCN in patients with spasticity to that of normal controls, there was no difference in the cross-sectional area of the nerve, but there was more variability in shape.Conclusions
Combined e-stim and ultrasound guidance during phenol neurolysis to the MCN allows a smaller volume of phenol to be used for equal effect, both at initial and repeat injection. The MCN shape was more variable in individuals with spasticity; this should be recognized so as to successfully locate the nerve to perform neurolysis.Level of Evidence
IV 相似文献35.
Hydroxychloroquine may be associated with reduced risk of coronary artery diseases in patients with rheumatoid arthritis: A nationwide population‐based cohort study 下载免费PDF全文
36.
Angiotensin 1‐7 modulates electrophysiological characteristics and calcium homoeostasis in pulmonary veins cardiomyocytes via MAS/PI3K/eNOS signalling pathway 下载免费PDF全文
Yen‐Yu Lu Wen‐Shiann Wu Yung‐Kuo Lin Chen‐Chuan Cheng Yao‐Chang Chen Shih‐Ann Chen Yi‐Jen Chen 《European journal of clinical investigation》2018,48(1)
Background
Atrial fibrillation (AF) is the most common sustained arrhythmia, and pulmonary veins (PVs) play a critical role in triggering AF. Angiotensin (Ang)‐(1‐7) regulates calcium (Ca2+) homoeostasis and also plays a critical role in cardiovascular pathophysiology. However, the role of Ang‐(1‐7) in PV arrhythmogenesis remains unclear.Materials and methods
Conventional microelectrodes, whole‐cell patch‐clamp and the fluo‐3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca2+ in isolated rabbit PV preparations and in single isolated PV cardiomyocytes, before and after administration of Ang‐(1‐7).Results
Ang (1‐7) concentration dependently (0.1, 1, 10 and 100 nmol/L) decreased PV spontaneous electrical activity. Ang‐(1‐7) (100 nmol/L) decreased the late sodium (Na+), L‐type Ca2+ and Na+‐Ca2+ exchanger currents, but did not affect the voltage‐dependent Na+ current in PV cardiomyocytes. In addition, Ang‐(1‐7) decreased intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. A779 (a Mas receptor blocker, 3 μmol/L), L‐NAME (a NO synthesis inhibitor, 100 μmol/L) or wortmannin (a specific PI3K inhibitor, 10 nmol/L) attenuated the effects of Ang‐(1‐7) (100 nmol/L) on PV spontaneous electric activity.Conclusion
Ang‐(1‐7) regulates PV electrophysiological characteristics and Ca2+ homoeostasis via Mas/PI3K/eNOS signalling pathway. 相似文献37.
Jaeki Jeong Haeyeon Kim Yung Jin Yoon Bright Walker Seyeong Song Jungwoo Heo Song Yi Park Jae Won Kim Gi-Hwan Kim Jin Young Kim 《RSC advances》2018,8(43):24110
We herein demonstrate n-i-p-type planar heterojunction perovskite solar cells employing spin-coated ZnO nanoparticles modified with various alkali metal carbonates including Li2CO3, Na2CO3, K2CO3 and Cs2CO3, which can tune the energy band structure of ZnO ETLs. Since these metal carbonates doped on ZnO ETLs lead to deeper conduction bands in the ZnO ETLs, electrons are easily transported from the perovskite active layer to the cathode electrode. The power conversion efficiency of about 27% is improved due to the incorporation of alkali carbonates in ETLs. As alternatives to TiO2 and n-type metal oxides, electron transport materials consisting of doped ZnO nanoparticles are viable ETLs for efficient n-i-p planar heterojunction solar cells, and they can be used on flexible substrates via roll-to-roll processing.Planar formamidinium perovskite solar cells have been fabricated with an alkali carbonate-doped zinc oxide layer. 相似文献
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