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Andrea Ciammola MD Jenny Sassone PhD Monica Sciacco MD Niccolò E. Mencacci MD Michela Ripolone PhD Caterina Bizzi MD Clarissa Colciago PhD Maurizio Moggio MD Gianfranco Parati MD Vincenzo Silani MD Gabriella Malfatto MD 《Movement disorders》2011,26(1):130-137
Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty‐five HD subjects and twenty‐five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise. © 2010 Movement Disorder Society 相似文献
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Francesco D’Angelo Laura Antolino Alessio Farcomeni Dario Sirimarco Andrea Kazemi Nava Martina De Siena Niccolò Petrucciani Giuseppe Nigri Stefano Valabrega Paolo Aurello Giovanni Ramacciato 《Medical oncology (Northwood, London, England)》2017,34(5):85
Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16–18.26 months); for resected patients OS was 22.78 months (95% CI 20.42–25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84–10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting. 相似文献
45.
Etiology of Syncope and Unexplained Falls in Elderly Adults with Dementia: Syncope and Dementia (SYD) Study 下载免费PDF全文
Andrea Ungar MD PhD Chiara Mussi MD PhD Alice Ceccofiglio MD Giuseppe Bellelli MD PhD Franco Nicosia MD Mario Bo MD Daniela Riccio MD Anna Maria Martone MD Livia Guadagno MD Gabriele Noro MD Giulia Ghidoni MD Martina Rafanelli MD Niccolò Marchionni MD Pasquale Abete MD PhD 《Journal of the American Geriatrics Society》2016,64(8):1567-1573
46.
Niccolò Sturli Giuseppe Lonetto Fabiana Rosati Bruno Jim Rocca Giuseppina Ventimiglia Maria Teresa del Vecchio Igor Prudovsky Niccolò Marchionni Francesca Tarantini 《International journal of cancer. Journal international du cancer》2013,133(11):2577-2586
Prostate cancer (PC) is still the second cause of cancer‐related death among men. Although patients with metastatic presentation have an ominous outcome, the vast majority of PCs are diagnosed at an early stage. Nonetheless, even among patients with clinically localized disease the outcome may vary considerably. Other than androgen sensitivity, little is known about which other signaling pathways are deranged in aggressive, localized cancers. The elucidation of such pathways may help to develop innovative therapies aimed at specific molecular targets. We report that in a hormone‐sensitive PC cell line, LNCaP, Notch3 was activated by hypoxia and sustained cell proliferation and colony formation in soft agar. Hypoxia also modulated cellular cholesterol content and the number and size of lipid rafts, causing a coalescence of small rafts into bigger clusters; under this experimental condition, Notch3 migrated from the non‐raft into the raft compartment where it colocalized with the γ‐secretase complex. We also looked at human PC biopsies and found that expression of Notch3 positively correlated with Gleason score and with expression of carbonic anhydrase IX, a marker of hypoxia. In conclusion, hypoxia triggers the activation of Notch3, which, in turn, sustains proliferation of PC cells. Notch3 pathway represents a promising target for adjuvant therapy in patients with PC. 相似文献
47.
Serena Lattante Mario Sabatelli Giulia Bisogni Giuseppe Marangi Paolo Niccolò Doronzio Francesco Martello Anna Gloria Renzi Elda Del Giudice Alberta Leon Paola Cimbolli Daniela Marchione Umberto Costantino Gabriele Lucioli Daniela Bernardo Emiliana Meleo Agata Katia Patanella Angela Romano Marcella Zollino Amelia Conte 《European journal of neurology》2023,30(5):1246-1255
Background and objectives
Genetic variants in the gene TARDBP, encoding TDP-43 protein, are associated with amyotrophic lateral sclerosis (ALS) in familial (fALS) and sporadic (sALS) cases. Objectives of this study were to assess the contribution of TARDBP in a large cohort of Italian ALS patients, to determine the TARDBP-associated clinical features and to look for genotype–phenotype correlation and penetrance of the mutations.Methods
A total of 1992 Italian ALS patients (193 fALS and 1799 sALS) were enrolled in this study. Sanger sequencing of TARDBP gene was performed in patients and, when available, in patients' relatives.Results
In total, 13 different rare variants were identified in 43 index cases (10 fALS and 33 sALS) with a cumulative mutational frequency of 2.2% (5.2% of fALS, 1.8% of sALS). The most prevalent variant was the p.A382T followed by the p.G294V. Cognitive impairment was detected in almost 30% of patients. While some variants, including the p.G294V and the p.G376D, were associated with restricted phenotypes, the p.A382T showed a marked clinical heterogeneity regarding age of onset, survival and association with cognitive impairment. Investigations in parents, when possible, showed that the variants were inherited from healthy carriers and never occurred de novo.Conclusions
In our cohort, TARDBP variants have a relevant frequency in Italian ALS patients and they are significantly associated with cognitive impairment. Clinical presentation is heterogeneous. Consistent genotype–phenotype correlations are limited to some mutations. A marked phenotypic variability characterizes the p.A382T variant, suggesting a multifactorial/oligogenic pathogenic mechanism. 相似文献48.
Niccolò Di Giosaffatte Irene Bottillo Luigi Laino Giovanni Iaquinta Alessandro Ferraris Mariagrazia Garzia Simone Bargiacchi Claudia Mulargia Maria Rosaria Angelitti Fabiana Palumbo Barbara Grammatico Cinzia Bartolelli Maria Giovanna Salerno Luigi Rigacci Paola Grammatico 《Prenatal diagnosis》2022,42(8):1000-1003
49.
Camarlinghi N Gori I Retico A Bellotti R Bosco P Cerello P Gargano G Lopez Torres E Megna R Peccarisi M Fantacci ME 《International journal of computer assisted radiology and surgery》2012,7(3):455-464
Purpose
The aim of this work is to evaluate the potential of combining different computer-aided detection (CADe) methods to increase the actual support for radiologists of automated systems in the identification of pulmonary nodules in CT scans.Methods
The outputs of three different CADe systems developed by researchers of the Italian MAGIC-5 collaboration were combined. The systems are: the CAMCADe (based on a Channeler-Ant-Model which segments vessel tree and nodule candidates and a neural classifier), the RGVPCADe (a Region-Growing- Volume-Plateau algorithm detects nodule candidates and a neural network reduces false positives); the VBNACADe (two dedicated procedures, based respectively on a 3D dot-enhancement algorithm and on intersections of pleura surface normals, identifies internal and juxtapleural nodules, and a Voxel-Based-Neural-Approach reduces false positives. A dedicated OsiriX plugin implemented with the Cocoa environments of MacOSX allows annotating nodules and visualizing singles and combined CADe findings.Results
The combined CADe has been tested on thin slice (lower than 2?mm) CTs of the LIDC public research database and the results have been compared with those obtained by the single systems. The FROC (Free Receiver Operating Characteristic) curves show better results than the best of the single approaches.Conclusions
Has been demonstrated that the combination of different approaches offers better results than each single CADe system. A clinical validation of the combined CADe as second reader is being addressed by means of the dedicated OsiriX plugin. 相似文献50.