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121.
Katrina Hueniken MPH Catriona M. Douglas BSc MBChB MD Ashok R. Jethwa MD Maryam Mirshams MSc Lawson Eng MD Andrew Hope MD Douglas B. Chepeha MD David P. Goldstein MD MSc Jolie Ringash MD MSc Aaron Hansen BSc MBBS Rosemary Martino PhD Madeline Li MD PhD Geoffrey Liu MD Wei Xu MD John R. de Almeida MD MSc 《Cancer》2020,126(17):4042-4050
122.
Angèle Nalbandian Arif A. Khan Ruchi Srivastava Katrina J. Llewellyn Baichang Tan Nora Shukr Yasmin Fazli Virginia E. Kimonis Lbachir BenMohamed 《Inflammation》2017,40(1):21-41
Aberrant activation of the NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, triggers a pathogenic inflammatory response in many inherited neurodegenerative disorders. Inflammation has recently been associated with valosin-containing protein (VCP)-associated diseases, caused by missense mutations in the VCP gene. This prompted us to investigate whether NLRP3 inflammasome plays a role in VCP-associated diseases, which classically affects the muscles, bones, and brain. In this report, we demonstrate (i) an elevated activation of the NLRP3 inflammasome in VCP myoblasts, derived from induced pluripotent stem cells (iPSCs) of VCP patients, which was significantly decreased following in vitro treatment with the MCC950, a potent and specific inhibitor of NLRP3 inflammasome; (ii) a significant increase in the expression of NLRP3, caspase 1, IL-1β, and IL-18 in the quadriceps muscles of VCPR155H/+ heterozygote mice, an experimental mouse model that has many clinical features of human VCP-associated myopathy; (iii) a significant increase of number of IL-1β(+)F4/80(+)Ly6C(+) inflammatory macrophages that infiltrate the muscles of VCPR155H/+ mice; (iv) NLRP3 inflammasome activation and accumulation IL-1β(+)F4/80(+)Ly6C(+) macrophages positively correlated with high expression of TDP-43 and p62/SQSTM1 markers of VCP pathology in damaged muscle; and (v) treatment of VCPR155H/+ mice with MCC950 inhibitor suppressed activation of NLRP3 inflammasome, reduced the F4/80(+)Ly6C(+)IL-1β(+) macrophage infiltrates in the muscle, and significantly ameliorated muscle strength. Together, these results suggest that (i) NLRP3 inflammasome and local IL-1β(+)F4/80(+)Ly6C(+) inflammatory macrophages contribute to pathogenesis of VCP-associated myopathy and (ii) identified MCC950 specific inhibitor of the NLRP3 inflammasome with promising therapeutic potential for the treatment of VCP-associated myopathy. 相似文献
123.
Jacqueline Schoumans Javier Suela Ros Hastings Dominique Muehlematter Katrina Rack Eva van den Berg H. Berna Beverloo Marian Stevens‐Kroef 《Genes, chromosomes & cancer》2016,55(5):480-491
Genetic profiling is important for disease evaluation and prediction of prognosis or responsiveness to therapy in neoplasia. Microarray technologies, including array comparative genomic hybridization and single‐nucleotide polymorphism‐detecting arrays, have in recent years been introduced into the diagnostic setting for specific types of haematological malignancies and solid tumours. It can be used as a complementary test or depending on the neoplasia investigated, also as a standalone test. However, comprehensive and readable presentation of frequently identified complex genomic profiles remains challenging. To assist diagnostic laboratories, standardization and minimum criteria for clinical interpretation and reporting of acquired genomic abnormalities detected through arrays in neoplastic disorders are presented. © 2016 Wiley Periodicals, Inc. 相似文献
124.
Izak J. Bisschoff Christine Zeschnigk Denise Horn Brigitte Wellek Angelika Rieß Maja Wessels Patrick Willems Peter Jensen Andreas Busche Jens Bekkebraten Maya Chopra Hanne Dahlgaard Hove Christina Evers Ketil Heimdal Ann‐Sophie Kaiser Erdmut Kunstmann Kristina Lagerstedt Robinson Maja Linné Patricia Martin James McGrath Winnie Pradel Katrina E. Prescott Bernd Roesler Gorazd Rudolf Ulrike Siebers‐Renelt Nataliya Tyshchenko Dagmar Wieczorek Gerhard Wolff William B. Dobyns Deborah J. Morris‐Rosendahl 《Human mutation》2013,34(1):237-247
OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X‐linked condition with lethality in males. Mutations in OFD1 also cause X‐linked Joubert syndrome (JBTS10) and Simpson–Golabi–Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnostic criteria. A first, detailed evaluation of brain MRIs from seven patients with cognitive defects illustrated extensive variability with the complete brain phenotype consisting of complete agenesis of the corpus callosum, large single or multiple interhemispheric cysts, striking cortical infolding of gyri, ventriculomegaly, mild molar tooth malformation and moderate to severe cerebellar vermis hypoplasia. Although the OFD1 gene apparently escapes X‐inactivation, skewed inactivation was observed in seven of 14 patients. The direction of skewing did not correlate with disease severity, reinforcing the hypothesis that additional factors contribute to the extensive intrafamilial variability. 相似文献
125.
Katrina J Light Peter R Joyce Suzanne E Luty Roger T Mulder Christropher M A Frampton Laura R M Joyce Allison L Miller Martin A Kennedy 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(4):409-413
We have previously reported that the Ser9Gly dopamine D3 receptor (DRD3) polymorphism was associated with increased rates of obsessive-compulsive personality disorder (OCPD) symptomology. We tested the replicability of this association within a further two independent groups of individuals with a history of depression, from a clinical sample (n = 149) and a family study (n = 213). The data from the replication samples and the original sample, within which the association was found, were compiled within a meta-analysis. Although the independent samples did not replicate the original finding, the meta-analysis elucidated significant evidence supporting the association. An individual with Gly/Gly genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD. Male gender was also found to be a significant predictor of OCPD diagnosis (OR = 2.82, P = 0.001). An exploration of an association of DRD3 with Axis I anxiety disorder diagnoses and Temperament and Character Inventory (TCI) traits, in particular persistence, revealed no support for an association. We conclude that DRD3 may contribute to the development of OCPD. 相似文献
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128.
Arck PC Rücke M Rose M Szekeres-Bartho J Douglas AJ Pritsch M Blois SM Pincus MK Bärenstrauch N Dudenhausen JW Nakamura K Sheps S Klapp BF 《Reproductive biomedicine online》2008,17(1):101-113
Many pregnancies are lost during early gestation, but clinicians still lack tools to recognize risk factors for miscarriage. Thus, the identification of risk factors for miscarriage during the first trimester in women with no obvious risk for a pregnancy loss was the aim of this prospective cohort trial. A total of 1098 women between gestation weeks 4 and 12 in whom no apparent signs of a threatened pregnancy could be diagnosed were recruited. Demographic, anamnestic, psychometric and biological data were documented at recruitment and pregnancy outcomes were registered subsequently. Among the cases with sufficiently available data, 809 successfully progressing pregnancies and 55 subsequent miscarriages were reported. In this cohort, risk of miscarriage was significantly increased in women at higher age (>33 years), lower body mass index (< or =20 kg/ m(2)) and lower serum progesterone concentrations (< or =12 ng/ml) prior to the onset of the miscarriage. Women with subsequent miscarriage also perceived higher levels of stress/demands (supported by higher concentrations of corticotrophin-releasing hormone) and revealed reduced concentrations of progesterone-induced blocking factor. These risk factors were even more pronounced in the subcohort of women (n = 335) recruited between gestation weeks 4 and 7. The identification of these risk factors and development of an interaction model of these factors, as introduced in this article, will help clinicians to recognize pregnant women who require extra monitoring and who might benefit from therapeutic interventions such as progestogen supplementation, especially during the first weeks of pregnancy, to prevent a miscarriage. 相似文献
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130.
The BioFIND study: Characteristics of a clinically typical Parkinson's disease biomarker cohort
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Un Jung Kang MD Jennifer G. Goldman MD MS Roy N. Alcalay MD MS Tao Xie MD PhD Paul Tuite MD Claire Henchcliffe MD DPhil Penelope Hogarth MD Amy W. Amara MD PhD Samuel Frank MD Alice Rudolph PhD Cynthia Casaceli MBA Howard Andrews PhD Katrina Gwinn MD Margaret Sutherland PhD Catherine Kopil PhD Lona Vincent MPH Mark Frasier PhD 《Movement disorders》2016,31(6):924-932