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51.
Antonio Cerasa Aldo Quattrone Fabrizio Piras Graziella Mangone Angela Magariello Sabrina Fagioli Paolo Girardi Maria Muglia Carlo Caltagirone Gianfranco Spalletta 《Social cognitive and affective neuroscience》2014,9(10):1537-1545
Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into ‘no anxiety’ and ‘subclinical anxiety’ groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours. 相似文献
52.
From the Cover: Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2
Efrat Gabai-Kapara Amnon Lahad Bella Kaufman Eitan Friedman Shlomo Segev Paul Renbaum Rachel Beeri Moran Gal Julia Grinshpun-Cohen Karen Djemal Jessica B. Mandell Ming K. Lee Uziel Beller Raphael Catane Mary-Claire King Ephrat Levy-Lahad 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(39):14205-14210
In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.Inherited mutations in BRCA1 and BRCA2 predispose to high risks of breast and ovarian cancer. Among female mutation carriers, presymptomatic surgical measures significantly reduce morbidity and mortality (1, 2). In particular, risk-reducing salpingo-oophorectomy (i.e., the removal of ovaries and fallopian tubes from a woman without ovarian cancer) reduces risk both of breast cancer and of ovarian cancer, as well as overall mortality (1). However, for many mutation carriers identified following their first cancer diagnosis, genetic testing was not previously indicated because family history did not suggest inherited cancer predisposition (3–5, 6). From a prevention perspective, it is a missed opportunity to identify a woman as a BRCA1 or BRCA2 mutation carrier only after she develops cancer.Among Ashkenazi (European) Jews (AJ), three mutations, BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, account for the great majority of inherited cancer risk due to BRCA1 and BRCA2 (7). In the AJ population, 2.5% of persons carry one of these three mutations (8), and the mutations account for 11% of breast cancer (3) and 40% of ovarian cancer (9, 10). These observations suggest that genetic testing in the AJ population for these mutations fulfills WHO criteria for population screening (11, 12): The disease is an important public health burden to the target population; prevalence and attributable risk of disease due to the mutations are known; and effective interventions exist. However, one necessary piece of information remains unknown: What is the disease risk to mutation carriers ascertained from the general population, rather than carriers identified based on family history (13)?Previous studies assessing cancer risks due to mutations in BRCA1 and BRCA2 ascertained carriers through high-incidence families (14), through a single index case with breast or ovarian cancer (3, 15) or through both affected and unaffected carriers (16). In a 1997 study of AJ volunteers, most index cases had no previous cancer diagnosis, but the percentage of index cases with a family history of breast cancer was approximately double that of unselected AJs (17). In principle, these strategies could have yielded risk estimates different from those of carriers ascertained from the local host population, if cancer risk in BRCA1 or BRCA2 carriers were influenced by familial factors other than the BRCA1 or BRCA2 mutation, such as modifier genes or shared environment (18). In addition, in almost all of these studies, risk estimates were based on imputing carrier status, rather than on direct genetic testing of BRCA1 and BRCA2. This year, the Recommendation Statement on BRCA Testing from the US Preventive Services Task Force recommended against population screening for BRCA1 and BRCA2 mutations, because cancer risk to mutation carriers in the general population was not yet known (19). To address this gap, in this study we assessed breast and ovarian cancer risks in confirmed carriers of BRCA1 and BRCA2 mutations ascertained from the general population. The study was undertaken in the AJ population, because screening for only three founder mutations is sufficient to capture nearly all inherited cancer risk in this population due to BRCA1 and BRCA2 (7). 相似文献
53.
54.
Domenico Angelucci Nicola Tinari Antonino Grassadonia Ettore Cianchetti Giampiero Ausili-Cefaro Laura Iezzi Marinella Zilli Simona Grossi Lucia Anna Ursini Maria Teresa Scognamiglio Graziella Castrilli Michele De Tursi Paolo Noccioli Pasquale Cioffi Stefano Iacobelli Clara Natoli 《Journal of cancer research and clinical oncology》2013,139(2):269-280
Purpose
The aim of this study is to evaluate the long-term outcome of patients with locally advanced breast cancer treated with neoadjuvant systemic chemotherapy (NST) in routine clinical practice.Methods
Four hundred and nine patients were identified between January 1999 and December 2011. All patients received NST followed by surgery, adjuvant treatments and radiotherapy, as appropriate.Results
At Kaplan–Meier analysis, patients with surgical stage III disease were more likely to develop distant metastasis and die from breast cancer (p < 0.001). Luminal A and luminal B/HER2-negative patients had better prognosis; moreover, patients with hormone receptor (HR)-positive tumors had a significantly longer DRFS (p < 0.0049) and OS (p < 0.0001) compared with patients with HR-negative tumors as well as patients who underwent breast-conserving surgery (DRFS and OS: p < 0.001). In multivariate analysis, HR negativity (p < 0.001 for both DRFS and OS), mastectomy (DRFS: p = 0.009; OS: p = 0.05) and stage III disease (DRFS: p < 0.001; OS: p = 0.003) were associated with shorter DRFS and OS.Conclusions
HR negativity, mastectomy and pathological stage III disease are the variables independently associated with a worse outcome in our cohort of patients. These data are of high interest since they derive from a very heterogeneous group of patients, treated with different neoadjuvant/adjuvant regimens outside of clinical trials and with a long follow-up period. 相似文献55.
Violetta Insolia Erica C. Priori Caterina Gasperini Federica Coppa Marco Cocchia Erika Iervasi Beatrice Ferrari Roberta Besio Silvia Maruelli Graziella Bernocchi Antonella Forlino Maria G. Bottone 《The Journal of comparative neurology》2020,528(1):65-84
The extracellular matrix is essential for brain development, lamination, and synaptogenesis. In particular, the basement membrane below the pial meninx (pBM) is required for correct cortical development. The last step in the catabolism of the most abundant protein in pBM, collagen Type IV, requires prolidase, an exopeptidase cleaving the imidodipeptides containing pro or hyp at the C-terminal end. Mutations impairing prolidase activity lead in humans to the rare disease prolidase deficiency characterized by severe skin ulcers and mental impairment. Thus, the dark-like (dal) mouse, in which the prolidase is knocked-out, was used to investigate whether the deficiency of prolidase affects the neuronal maturation during development of a brain cortex area. Focusing on the cerebellar cortex, thinner collagen fibers and disorganized pBM were found. Aberrant cortical granule cell proliferation and migration occurred, associated to defects in brain lamination, and in particular in maturation of Purkinje neurons and formation of synaptic contacts. This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency. 相似文献
56.
Zumel-Marne Angela Kundi Michael Castaño-Vinyals Gemma Alguacil Juan Petridou Eleni Th Georgakis Marios K. Morales-Suárez-Varela Maria Sadetzki Siegal Piro Sara Nagrani Rajini Filippini Graziella Hutter Hans-Peter Dikshit Rajesh Woehrer Adelheid Maule Milena Weinmann Tobias Krewski Daniel ′t Mannetje Andrea Momoli Franco Lacour Brigitte Mattioli Stefano Spinelli John J. Ritvo Paul Remen Thomas Kojimahara Noriko Eng Amanda Thurston Angela Lim Hyungryul Ha Mina Yamaguchi Naohito Mohipp Charmaine Bouka Evdoxia Eastman Chelsea Vermeulen Roel Kromhout Hans Cardis Elisabeth 《Journal of neuro-oncology》2020,147(2):427-440
Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in... 相似文献
57.
Aim: Dentistry is a stressful and exhausting profession with high levels of burnout. Sensory processing sensitivity (SPS) is a basic personality trait characterised by a gradient of sensitivity to both internal and external stimuli, including social and emotional cues. In this study, the influence of SPS on burnout and professional quality of life among Israeli dentists was analysed. Methods: Two-hundred and forty-three Israeli dentists responded to questionnaires that collected information on their SPS and professional quality of life (burnout, satisfaction at work and level of secondary traumatic stress), as well demographic variables, professional specialisation and workload. Results: Linear regression analyses showed that burnout can be predicted by the three aspects of SPS (ease of excitation, low sensory threshold and aesthetic sensitivity; 32% of the variance). Additionally, the same three aspects of SPS also predicted dentists’ satisfaction at work (24% of the variance). Ease of excitation and low sensory threshold, but not aesthetic sensitivity, predicted dentists’ reaction to their patients’ stress and trauma (23% of the variance). Conclusions: Sensory processing sensitivity can serve as a tool to identify dentists who are prone to develop burnout and whose professional quality of life can be adversely affected by their profession.Key words: Dentistry, sensory processing sensitivity, burnout, secondary traumatic stress, professional quality of life, compassion satisfaction 相似文献
58.
L. Chiapparini G. Uziel C. Vallinoto M. G. Bruzzone A. Rovelli G. Tricomi A. Bizzi N. Nardocci C. Rizzari M. Savoiardo 《Neurological sciences》2011,32(3):473-477
Hemophagocytic lymphohistiocytosis (HLH) is a rare disease with rarer neurological presentation. When this occurs, diagnosis
may be delayed. This report aims to call attention to clinical, laboratory, and radiological features that should prompt the
correct diagnosis. A 13-year-old girl presented with progressive increase in intracranial pressure and ataxia. MRI showed
a diffuse tumor-like swelling of the cerebellum with tonsillar herniation and patchy white matter post-contrast enhancement.
Regression of swelling with steroids ruled out glioma and medulloblastoma, and brain lymphoma was considered. Diagnosis of
HLH was reached 2 months after onset when uncontrolled fever and severe elevation of liver enzymes occurred. Two bone marrow
biopsies were needed to demonstrate hemophagocytosis. Familial HLH was confirmed by perforin gene mutations. Bone marrow transplantation
was performed. The early diagnosis of HLH may be life saving. Awareness of the disease is necessary to investigate its characteristic
findings, thus avoiding a delay in diagnosis. 相似文献
59.
Edna Aparecida Ferraz de Araújo Navas Aline Cássia Inocêncio Janete Dias Almeida Graziella Nuernberg Back-Brito Adolfo José Mota Antonio Olavo Cardoso Jorge Silvia Maria Rodrigues Querido Ivan Balducci Cristiane Yumi Koga-Ito 《Journal of oral pathology & medicine》2009,38(10):764-767
Objective: The aim of this study was to evaluate the prevalence of Candida spp. and presence of oral lesions in Brazilian leprosy patients under multidrug therapy (MDT).
Methods: Thirty-eight individuals (18 males and 20 females, median age 53 years) clinically and microbiologically diagnosed as leprosy (lepromatous variant), and under MDT for at least 45 days were studied. The control group constituted by 38 healthy individuals (median age 53.5), matched to the test group in relation to age, gender and oral conditions. Oral rinses were collected and the Candida identification was performed by phenotypic tests. The existence of Candida dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Twenty-nine leprosy patients were examined intra-orally for the presence of lesions. Data were analyzed by z- and Mann–Whitney tests (α = 5%).
Results: Yeast carriage rate between leprosy patients (65.8%) and controls (47.4%) was similar ( P = 0.099), and no significant difference between yeast counts was observed ( P = 0.1004). Candida albicans was the most frequently isolated species in both groups. In the leprosy group, Candida tropicalis and Candida parapsilosis were also identified. In the control group, we additionally identified Candida tropicalis , Candida glabrata and Candida kefyr. Candida dubliniensis was not detected. No leprosy-related oral lesion was registered.
Conclusion: Within the limits of the study, we concluded that Brazilian leprosy patients under MDT showed similar levels of carriage and Candida species distribution in relation to the controls. 相似文献
Methods: Thirty-eight individuals (18 males and 20 females, median age 53 years) clinically and microbiologically diagnosed as leprosy (lepromatous variant), and under MDT for at least 45 days were studied. The control group constituted by 38 healthy individuals (median age 53.5), matched to the test group in relation to age, gender and oral conditions. Oral rinses were collected and the Candida identification was performed by phenotypic tests. The existence of Candida dubliniensis among the isolates was analyzed using a validated multiplex PCR assay. Twenty-nine leprosy patients were examined intra-orally for the presence of lesions. Data were analyzed by z- and Mann–Whitney tests (α = 5%).
Results: Yeast carriage rate between leprosy patients (65.8%) and controls (47.4%) was similar ( P = 0.099), and no significant difference between yeast counts was observed ( P = 0.1004). Candida albicans was the most frequently isolated species in both groups. In the leprosy group, Candida tropicalis and Candida parapsilosis were also identified. In the control group, we additionally identified Candida tropicalis , Candida glabrata and Candida kefyr. Candida dubliniensis was not detected. No leprosy-related oral lesion was registered.
Conclusion: Within the limits of the study, we concluded that Brazilian leprosy patients under MDT showed similar levels of carriage and Candida species distribution in relation to the controls. 相似文献
60.