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The detection of rare deleterious variants is the preeminent current technical challenge in statistical genetics. Sorting the deleterious from neutral variants at a disease locus is challenging because of the sparseness of the evidence for each individual variant. Hierarchical modeling and Bayesian model uncertainty are two techniques that have been shown to be promising in pinpointing individual rare variants that may be driving the association. Interpreting the results from these techniques from the perspective of multiple testing is a challenge and the goal of this article is to better understand their false discovery properties. Using simulations, we conclude that accurate false discovery control cannot be achieved in this framework unless the magnitude of the variants' risk is large and the hierarchical characteristics have high accuracy in distinguishing deleterious from neutral variants. 相似文献
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Irina Todorova Anna Alexandrova-Karamanova Yulia Panayotova Elitsa Dimitrova Tatyana Kotzeva 《International journal of behavioral medicine》2014,21(1):29-36
Background
New preventive technologies such as vaccines offer insight into psychological, social, and cultural landscapes. Providers have a key role in parents' decisions for vaccinating their children. Yet, perspectives from providers regarding the human papillomavirus (HPV) vaccine, or vaccination in general, are rarely soughtPurpose
Our objective in this paper is to understand how the HPV vaccine is perceived by health care providers and the multiple contextual meanings it elicits.Methods
We conducted interviews with 20 health care professionals in Bulgaria about their attitudes and practices related to HPV vaccination and their recommendations for policies. The verbatim-transcribed interviews were analyzed through narrative analysis, with a special focus on language.Results
We illustrate providers' contradictory and contextualized constructions of the vaccine and the narrative strategies they use to manage any uncertainty it elicits. These include being advocates and missionaries for preventive health, confirming their trust in the medical profession and professional organizations, challenging patients' concerns with rational explanations, normalizing the risk of medical innovations, and avoiding the sexual nature of HPV transmission.Conclusions
The introduction of a vaccine to prevent HPV infection, and by implication, possibly cervical and other cancers, created hope, and at the same time, intensified confusion and uncertainty. Providers have been frustrated for years with the rising mortality from cervical cancer in Bulgaria, and their perceived powerlessness in affecting this. HPV vaccination, on the other hand, seems relatively simple and “taming uncertainty” positions them as instrumental in limiting (or even eliminating) morbidity and mortality in future generations. 相似文献4.
Caitlin A. McIntyre MD Sharon A. Lawrence MD Allison L. Richards PhD Joanne F. Chou MPH Winston Wong MD Marinela Capanu PhD Michael F. Berger PhD Mark T. A. Donoghue PhD Kenneth H. Yu MD Anna M. Varghese MD David P. Kelsen MD Wungki Park MD Vinod P. Balachandran MD T. Peter Kingham MD Michael I. D’Angelica MD Jeffrey A. Drebin MD PhD William R. Jarnagin MD Christine A. Iacobuzio-Donahue MD PhD Peter J. Allen MD Eileen M. O’Reilly MD 《Cancer》2020,126(17):3939-3949
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Åke Borg Robert W. Haile Kathleen E. Malone Marinela Capanu Ahn Diep Therese Törngren Sharon Teraoka Colin B. Begg Duncan C. Thomas Patrick Concannon Lene Mellemkjaer Leslie Bernstein Lina Tellhed Shanyan Xue Eric R. Olson Xiaolin Liang Jessica Dolle Anne‐Lise Børresen‐Dale Jonine L. Bernstein 《Human mutation》2010,31(3):E1200-E1240
BRCA1 and BRCA2 screening in women at high‐risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population‐based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA‐binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. © 2010 Wiley‐Liss, Inc. 相似文献
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Larisa Daniela Sandulescu Cristiana Marinela Urhut Sarmis Marian Sandulescu Ana-Maria Ciurea Sergiu Marian Cazacu Sevastita Iordache 《World journal of hepatology》2021,13(12):1892-1908
Hepatic hemangioma is usually detected on a routine ultrasound examination because of silent clinical behaviour. The typical ultrasound appearance of hemangioma is easily recognizable and quickly guides the diagnosis without the need for further investigation. But there is also an entire spectrum of atypical and uncommon ultrasound features and our review comes to detail these particular aspects. An atypical aspect in standard ultrasound leads to the continuation of explorations with an imaging investigation with contrast substance [ultrasound/ computed tomography/or magnetic resonance imaging (MRI)]. For a clinician who practices ultrasound and has an ultrasound system in the room, the easiest, fastest, non-invasive and cost-effective method is contrast enhanced ultrasound (CEUS). Approximately 85% of patients are correctly diagnosed with this method and the patient has the correct diagnosis in about 30 min without fear of malignancy and without waiting for a computer tomography (CT)/MRI appointment. In less than 15% of patients CEUS does not provide a conclusive appearance; thus, CT scan or MRI becomes mandatory and liver biopsy is rarely required. The aim of this updated review is to synthesize the typical and atypical ultrasound aspects of hepatic hemangioma in the adult patient and to propose a fast, non-invasive and cost-effective clinical-ultrasound algorithm for the diagnosis of hepatic hemangioma. 相似文献
8.
THE AIM OF THIS STUDY: Is to identify two severe complications after catheterism of nasolacrimal duct. A boy, 9 months old, was treated in Clinica I Oftalmologie la?i for presptal cellulitis after catheterism of nasolacrimal duct which was performed in other Eye clinic, without general anesthesia. Also, this child presented the rupture of punctal and inferior canalicular duct. CONCLUSION: Catheterism of nasolacrimal duct must be performed by ophthalmopediatric doctors with experience, under general anesthesia, to prevent complications. 相似文献
9.
Păsăreanu M Plămădeală P 《Revista medico-chirurgical?? a Societ????ii de Medici ??i Naturali??ti din Ia??i》2003,107(4):863-867
The aim of the study was the determination of the correlation between the morphostructural aspects of the enamel defects and the clinical diagnostic and the nosologic kinds of these diseases. The research was made on 600 children from Iassy between 7-11 years old, who were examined in natural light. The index used for the systematization of the data was EDS. We used 21 temporary teeth and we examined these teeth on an optic microscope. The study show that there is no absolute correlation between the morphostructural aspects of the enamel defects and the clinical aspects of the lesions, and the clinical defect may not be always associate to the dysplasia from the imperfect amelogenesis. 相似文献
10.
Hafner C Toll A Fernández-Casado A Earl J Marqués M Acquadro F Méndez-Pertuz M Urioste M Malats N Burns JE Knowles MA Cigudosa JC Hartmann A Vogt T Landthaler M Pujol RM Real FX 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(48):20780-20785
Malignant tumors result from the accumulation of genetic alterations in oncogenes and tumor suppressor genes. Much less is known about the genetic changes in benign tumors. Seborrheic keratoses (SK) are very frequent benign human epidermal tumors without malignant potential. We performed a comprehensive mutational screen of genes in the FGFR3-RAS-MAPK and phosphoinositide 3-kinase (PI3K)-AKT pathways from 175 SK, including multiple lesions from each patient. SK commonly harbored multiple bona fide oncogenic mutations in FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 oncogenes but not in tumor suppressor genes TSC1 and PTEN. Despite the occurrence of oncogenic mutations and the evidence for downstream ERK/MAPK and PI3K pathway signaling, we did not find induction of senescence or a DNA damage response. Array comparative genomic hybridization (aCGH) analysis revealed that SK are genetically stable. The pattern of oncogenic mutations and X chromosome inactivation departs significantly from randomness and indicates that spatially independent lesions from a given patient share a clonal relationship. Our findings show that multiple oncogenic mutations in the major signaling pathways involved in cancer are not sufficient to drive malignant tumor progression. Furthermore, our data provide clues on the origin and spread of oncogenic mutations in tissues, suggesting that apparently independent (multicentric) adult benign tumors may have a clonal origin. 相似文献