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1.
Evidence for the involvement of a Bemisia tabaci GroEL homologue in the transmission of tomato yellow leaf curl geminivirus (TYLCV) is presented. A approximately 63-kDa protein was identified in B. tabaci whole-body extracts using an antiserum raised against aphid Buchnera GroEL. The GroEL homologue was immunolocalized to a coccoid-shaped whitefly endosymbiont. The 30 N-terminal amino acids of the whitefly GroEL homologue showed 80% homology with that from different aphid species and GroEL from Escherichia coli. Purified GroEL from B. tabaci exhibited ultrastructural similarities to that of the endosymbiont from aphids and E. coli. In vitro ligand assays showed that tomato yellow leaf curl virus (TYLCV) particles displayed a specific affinity for the B. tabaci 63-kDa GroEL homologue. Feeding whiteflies anti-Buchnera GroEL antiserum before the acquisition of virions reduced TYLCV transmission to tomato test plants by >80%. In the haemolymph of these whiteflies, TYLCV DNA was reduced to amounts below the threshold of detection by Southern blot hybridization. Active antibodies were recovered from the insect haemolymph suggesting that by complexing the GoEL homologue, the antibody disturbed interaction with TYLCV, leading to degradation of the virus. We propose that GroEL of B. tabaci protects the virus from destruction during its passage through the haemolymph. 相似文献
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3.
The urge of identifying new pharmacological interventions to prevent or attenuate liver injury is of critical importance and needs an expanded experimental toolbox. Hepatocyte injury and cellular death is a prominent feature behind the pathology of liver diseases. Several research activities focused on identifying chemicals and hepatotoxicants that induce cell death by apoptosis, in addition to presenting its corresponding signaling pathway. Although such efforts provided further understanding of the mechanisms of cell death, it has also raised confusion concerning identifying the involvement of several modes of cell death including apoptosis, necrosis and fibrosis. The current review highlights the ability of several chemicals and potential hepatotoxicants to induce liver damage in rodents by means of apoptosis while the probable involvement of other modes of cell death is also exposed. Thus, several chemical substances including hepatotoxins, mycotoxins, hyperglycemia inducers, metallic nanoparticles and immunosuppressant drugs are reviewed to explore the hepatic cytotoxic spectrum they could exert on hepatocytes of rodents. In addition, the current review address the mechanism by which hepatotoxicity is initiated in hepatocytes in different rodents aiding the researcher in choosing the right animal model for a better research outcome. 相似文献
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5.
Breen DM Dolinsky VW Zhang H Ghanim H Guo J Mroziewicz M Tsiani EL Bendeck MP Dandona P Dyck JR Heximer SP Giacca A 《Atherosclerosis》2012,222(2):375-381
Revascularization procedures used for treatment of atherosclerosis often result in restenosis. Resveratrol (RSV), an antioxidant with cardiovascular benefits, decreases neointimal formation after arterial injury by a mechanism that is still not fully clarified. Our main objective was to address the role of nitric oxide synthases (NOSes) and more specifically the endothelial-NOS (eNOS) isoform as a mediator of this effect. RSV (4 mg/kg/day, s.c.) alone or in combination with the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) (2 mg/kg/day, s.c.) was given to Sprague-Dawley rats beginning at 3 days before arterial (carotid or aortic) injury. RSV reduced neointimal formation by 50% (P<0.01), decreased intimal cell proliferation by 37% (P<0.01) and reduced inflammatory markers such as PECAM and MMP-9 mRNA. These effects of RSV were all abolished by coadministration of l-NAME. Oral RSV (beginning at 5 days before arterial injury) reduced neointimal thickness after femoral wire injury in mice, however this effect was not observed in eNOS knockout mice. This is the first report of RSV decreasing neointimal cell proliferation and neointimal growth through an eNOS-dependent mechanism. 相似文献
6.
Ghanim H Monte SV Sia CL Abuaysheh S Green K Caruana JA Dandona P 《The Journal of clinical endocrinology and metabolism》2012,97(7):E1197-E1201
7.
Thao P. Nguyen Ali A. Sovari Arash Pezhouman Shankar Iyer Hong Cao Christopher Y. Ko Aneesh Bapat Nooshin Vahdani Mostafa Ghanim Michael C. Fishbein Hrayr S. Karagueuzian 《The Journal of physiology》2016,594(6):1689-1707
Key points
- Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.
- Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.
- Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.
- Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.
Abstract
Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H2O2; 0.15 mmol l−1). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H2O2 promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H2O2‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except with larger EAD amplitude. During the early stages of hypertension, when challenged with oxidative stress, SHR hearts showed an increased ventricular arrhythmogenicity that stems primarily from tissue remodelling (hypertrophy, fibrosis) rather than cellular electrophysiological changes. Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.Abbreviations
- AP
- action potential
- APD
- action potential duration
- APD90
- action potential at 90% duration
- CaMKII
- calcium/calmodulin‐dependent protein kinase II
- CaT
- calcium transient
- CaTD90
- calcium transient at 90% duration
- CI
- confidence interval
- DBP
- diastolic blood pressure
- EAD/DAD
- early/delayed after‐depolarization
- HR
- heart rate
- ICC
- interclass correlation
- ICa,L
- L‐type calcium current
- IKs
- slow delayed rectifier potassium current
- INa
- sodium current
- Ito
- transient outward potassium current
- IVS(d,s) interventricular septum thickness (during diastole
- during systole)
- LV
- left ventricle
- LVEF
- left ventricular ejection fraction
- LVFS
- left ventricular fractional shortening
- LVH
- left ventricular hypertrophy
- LVID(d,s) left ventricular internal diameter (during diastole
- during systole)
- MV
- mitral valve
- NR
- normotensive rats
- PA peak vel
- pulmonary artery peak velocity
- (P)CL
- (pacing) cycle length
- PW
- posterior wall
- P‐ECG
- pseudo‐electrocardiogram
- RV
- right ventricle
- RWT
- relative wall thickness
- SHR
- spontaneously hypertensive rats
- SHHF
- spontaneously hypertensive heart failure
- SBP
- systolic blood pressure
- VT/VF
- ventricular tachycardia and fibrillation
8.
Yehia Z. Alami Beesan T. Ghanim Sa’ed H. Zyoud 《Journal of occupational medicine and toxicology (London, England)》2018,13(1):21
Background
Resident doctors are continuously exposed to prolonged working hours and night shifts, making them susceptible to the many physical, psychological, and cognitive side effects of sleep deprivation, which may affect their quality of life. Therefore, this study aimed to determine the prevalence of sleep penury in resident doctors and to assess the association between self-apprehended sleepiness and quality of life.Methods
A cross-sectional study was carried out in the governmental hospitals in the North of the West Bank between May 2017 and September 2017. Doctors enrolled in residency programmes completed questionnaires about general, sociodemographic, and sleep characteristics. The doctors completed the Arabic Version of the Epworth Sleepiness Scale (ArESS) to assess subjective daytime sleepiness and the RAND 36-item short-form health survey (SF-36) to determine quality of life.Results
A total of 101 participants were enrolled. Daytime sleepiness was observed in 37.6% (n?=?38) of the participants with an ESS score of ≥10. There was a notable negative correlation between the ESS and quality of health index in the physical composition (r?=???0.351, p?<?0.001) demonstrated in the following four subscales: the physical functioning (p?<?0.001), role limitations due to physical health (p?=?0.045), body pain (p?=?0.036), and general health (p?<?0.001) components of the SF-36 scale. Females and residents of the centre region had poorer mental quality (p?=?0.006 and 0.020, respectively).Conclusions
More than one third of the resident doctors suffer from daytime sleepiness according to the ESS. This was proven to significantly affect several aspects of their quality of life, including physical function and health, body pain, and general health. Sleep deprivation and improvement of quality of life require health promotion actions among medical residents.9.
10.
Richard Gallon Harsh Sheth Christine Hayes Lisa Redford Ghanim Alhilal Ottilia O'Brien Helena Spiewak Amanda Waltham Ciaron McAnulty Osagie G. Izuogu Mark J. Arends Anca Oniscu Angel M. Alonso Sira M. Laguna Gillian M. Borthwick Mauro Santibanez‐Koref Michael S. Jackson John Burn 《Human mutation》2020,41(1):332-341
Microsatellite instability (MSI) testing of colorectal cancers (CRCs) is used to screen for Lynch syndrome (LS), a hereditary cancer‐predisposition, and can be used to predict response to immunotherapy. Here, we present a single‐molecule molecular inversion probe and sequencing‐based MSI assay and demonstrate its clinical validity according to existing guidelines. We amplified 24 microsatellites in multiplex and trained a classifier using 98 CRCs, which accommodates marker specific sensitivities to MSI. Sample classification achieved 100% concordance with the MSI Analysis System v1.2 (Promega) in three independent cohorts, totaling 220 CRCs. Backward–forward stepwise selection was used to identify a 6‐marker subset of equal accuracy to the 24‐marker panel. Assessment of assay detection limits showed that the 24‐marker panel is marginally more robust to sample variables than the 6‐marker subset, detecting as little as 3% high levels of MSI DNA in sample mixtures, and requiring a minimum of 10 template molecules to be sequenced per marker for >95% accuracy. BRAF c.1799 mutation analysis was also included to streamline LS testing, with all c.1799T>A variants being correctly identified. The assay, therefore, provides a cheap, robust, automatable, and scalable MSI test with internal quality controls, suitable for clinical cancer diagnostics. 相似文献