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1.
Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
Background
We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献2.
Coeli M. B. Lopes Tibor Rohács Gábor Czirják Tamás Balla Péter Enyedi Diomedes E. Logothetis 《The Journal of physiology》2005,564(1):117-129
Two-pore (2-P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5-bisphosphate (PIP2 ) gating underlies several aspects of 2-P channel regulation. Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP2 . We show that mechanical stimulation may promote PIP2 activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP2 hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP2 scavenger polylysine, and the inhibition by the phosphatidylinositol 4-kinase inhibitor wortmannin correlated with the level of agonist-induced inhibition. This finding suggests that the strength of channel PIP2 interactions determines the extent of PLC-induced inhibition. Finally, we show that PIP2 hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Our results suggest that PIP2 is a common gating molecule for K+ channel families despite their distinct structures and physiological properties. 相似文献
3.
L Csáthy I Pócsi L Kiss G Balla 《Acta paediatrica Academiae Scientiarum Hungaricae》1991,31(2):201-213
The authors investigated the urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the case of 101 normal healthy and 20 polycythemic newborns and prematures, and 50 prematures suffering from hypoxia on the 1st, 2nd, 4th, 14th, and 28th day after birth. The obtained activities were referred to the creatinine concentrations of the urine samples and given as NAG index. There were no significant differences in the NAG indices either between fullterm and preterm babies or between appropriate for gestational age (AGA) and small for gestational age (SGA) neonates of the normal group. The NAG indices on the first day of life were significantly higher in the case of polycythemic newborn in comparison with the normal group (p less than 0.01). On the 14th day, after the partial plasma exchange, the NAG indices returned to the normal range. The premature babies suffering from IRDS received an average 10.1 days oxygen supplementation. Their NAG indices were significantly (p less than 0.01) higher on the 1st, 2nd, 4th days than those of the healthy prematures of the normal group and decreased considerably up to the 14th day. Finally the NAG indices reached the normal value on the 28th day. These results support the assumption that the urinary NAG index is a suitable indicator of the renal tubular damage during the newborn period. 相似文献
4.
Vijay Gayam Venu M. Konala Srikanth Naramala Pavani Reddy Garlapati Mohamed A. Merghani Nirajan Regmi Mamtha Balla Sreedhar Adapa 《Journal of medical virology》2020,92(10):2181-2187
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace, and the World Health Organization declared it as pandemic on 11 March 2020. Mycoplasma pneumoniae is an "atypical" bacterial pathogen commonly known to cause respiratory illness in humans. The coinfection from SARS-CoV-2 and mycoplasma pneumonia is rarely reported in the literature to the best of our knowledge. We present a study in which 6 of 350 patients confirmed with COVID-19 were also diagnosed with M. pneumoniae infection. In this study, we described the clinical characteristics of patients with coinfection. Common symptoms at the onset of illness included fever (six [100%] patients); five (83.3%) patients had a cough, shortness of breath, and fatigue. The other symptoms were myalgia (66.6%), gastrointestinal symptoms (33.3%-50%), and altered mental status (16.7%). The laboratory parameters include lymphopenia, elevated erythrocyte sedimentation rate, C-reactive protein, lactate dehydrogenase, interleukin-6, serum ferritin, and D-dimer in all six (100%) patients. The chest X-ray at presentation showed bilateral infiltrates in all the patients (100%). We also described electrocardiogram findings, complications, and treatment during hospitalization in detail. One patient died during the hospital course. 相似文献
5.
Tony Wawina-Bokalanga Bert Vanmechelen Valentine Lhermitte Joan Martí-Carreras Valentijn Vergote Fara Raymond Koundouno Joseph Akoi-Bor Ruth Thom Tom Tipton Kimberley Steeds Kita Balla Moussa Ablam Amento Lies Laenen Sophie Duraffour Martin Gabriel Paula Ruibal Yper Hall Mandy Kader-Kond Stephan Günther Guy Baele Cesar Muoz-Fontela Johan Van Weyenbergh Miles W. Carroll Piet Maes 《Emerging infectious diseases》2021,27(1):76
We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD. 相似文献
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8.
Sudarshan Kumar Vijay M.D. D.M. Bhuwan Chandra Tiwari M.D. D.M. Mukul Misra M.D. D.M. Sudhanshu Kumar Dwivedi M.D. D.M. 《Echocardiography (Mount Kisco, N.Y.)》2014,31(1):E24-E26
The mitral valve aneurysm is a rare complication of infective endocarditis involving mitral or aortic valve. The perforation of the mitral valve aneurysm can lead to significant mitral regurgitation (MR) or thromboembolism, which can cause sudden hemodynamic deterioration. We describe here a case of healed infective endocarditis of the aortic valve with ruptured mitral valve aneurysm that led to severe MR. The aneurysm of the anterior mitral leaflet was diagnosed by two‐dimensional transthoracic echocardiography. In this case, three‐dimensional transthoracic echocardiography demonstrated the detailed morphology of mitral valve aneurysm which resulted in successful surgical repair of the aneurysm. 相似文献
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10.
Ferriporphyrins and endothelium: a 2-edged sword-promotion of oxidation and induction of cytoprotectants 总被引:4,自引:1,他引:4
Heme arginate infusions blunt the symptoms of patients with acute intermittent porphyria without evidence of the vascular or thrombotic side effects reported for hematin. To provide a rationale for heme arginate's safety, the present study examined the effects of various ferriporphyrins to sensitize human endothelial cells to free radical injury and to induce heme oxygenase and ferritin expression. Heme arginate, unlike hematin, did not amplify oxidant-induced cytotoxicity mediated by hydrogen peroxide (5.3 +/- 2.4 versus 62.3 +/- 5.3% (51)Cr release, P <.0001) or by activated neutrophils (14.4 +/- 2.9 versus 41.1 +/- 6.0%, P <.0001). Nevertheless, heme arginate efficiently entered endothelial cells similarly to hematin, since both markedly induced heme oxygenase mRNA (more than 20-fold increase) and enzyme activity. Even with efficient permeation, endothelial cell ferritin content was only minimally increased by heme arginate compared with a 10-fold induction by hematin; presumably less free iron was derived from heme arginate despite up-regulation of heme oxygenase. Hematin is potentially vasculopathic by its marked catalysis of oxidation of low-density lipoprotein (LDL) to endothelial-toxic moieties. Heme arginate was significantly less catalytic. Heme arginate-conditioned LDL was less than half as cytotoxic to endothelial cells as hematin-conditioned LDL (P <.004). It is concluded that heme arginate may be less vasculotoxic than hematin since it is an effective heme oxygenase gene regulator but a less efficient free-radical catalyst. 相似文献