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Montserrat Ruiz Mlina Bgou Nathalie Launay Pablo RaneaRobles Patrizia Bianchi Jone LpezErauskin Laia Morat Cristina Guilera Brengre Petit Catherine VaursBarriere Cline GuretGonthier MarieNoëlle BonnetDupeyron Stphane Fourcade Johan Auwerx Odile BoespflugTanguy Aurora Pujol 《Brain pathology (Zurich, Switzerland)》2018,28(5):611
Pelizaeus‐Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. The Plp1 overexpressing mouse model (PLP‐tg66/66) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan. The sequence of cellular events that cause neurodegeneration and ultimately death is poorly understood. In this work, we analyzed patient‐derived fibroblasts and spinal cords of the PLP‐tg66/66 mouse model, and identified redox imbalance, with altered antioxidant defense and oxidative damage to several enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We also evidenced malfunction of the mitochondria compartment with increased ROS production and depolarization in PMD patient''s fibroblasts, which was prevented by the antioxidant N‐acetyl‐cysteine. Finally, we uncovered an impairment of mitochondrial dynamics in patient''s fibroblasts which may help explain the ultrastructural abnormalities of mitochondria morphology detected in spinal cords from PLP‐tg66/66 mice. Altogether, these results underscore the link between redox and metabolic homeostasis in myelin diseases, provide insight into the pathophysiology of PMD, and may bear implications for tailored pharmacological intervention. 相似文献
43.
Early maladaptive schemas associated with dimensional and categorical psychopathology in patients with borderline personality disorder
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44.
Andrés Cabrera-León Antonio Daponte-Codina Inmaculada Mateo Elena Arroyo-Borrell Xavier Bartoll María José Bravo María Felicitas Domínguez-Berjón Gemma Renart Carlos Álvarez-Dardet Marc Marí-Dell’Olmo Julia Bolívar-Muñoz Marc Saez Vicenta Escribà-Agüir Laia Palència María José López Carme Saurina Vanessa Puig Unai Martín Mariola Bernal 《Gaceta sanitaria / S.E.S.P.A.S》2019,33(5):497
45.
Antonio Juli Francisco Blanco Benjamín Fernndez‐Gutierrez Antonio Gonzlez Juan D. Caete Joan Maym Mercedes Alperi‐Lpez Alex Oliv Hctor Corominas Víctor Martínez‐Taboada Isidoro Gonzlez-lvaro Antonio Fernandez‐Nebro Alba Erra Simn Snchez‐Fernndez Arnald Alonso María Lpez‐Lasanta Raül Tortosa Laia Cod Josep Lluis Gelpi Andrs C. García‐Montero Jaume Bertranpetit Devin Absher Richard M. Myers Jesús Tornero Sara Marsal 《Arthritis \u0026amp; Rheumatology》2016,68(6):1384-1391
46.
David Páez Laia Paré Albert Altés Francesc Josep Sancho-Poch Lourdes Petriz Jordi Garriga Josep Maria Monill Juliana Salazar Elisabeth del Rio Agustí Barnadas Eugenio Marcuello Montserrat Baiget 《Journal of cancer research and clinical oncology》2010,136(11):1681-1689
Purpose
Chemoradiotherapy using 5-fluorouracil has shown to be effective treatment for rectal cancer. Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. However, the predictive role of TS levels in early stage rectal cancer is not yet well understood. We analyzed the value of TS gene polymorphisms as a predictive marker in patients with stage II and III rectal cancer treated with preoperative concomitant radiotherapy and fluoropyrimidine-based chemotherapy.Methods and materials
Between 1998 and 2007, blood samples were obtained from 51 patients with stage II/III rectal cancer. Forty patients were T2–3 (78%), 11 were T4 (22%), and 59% were N+. DNA was extracted from peripheral blood, and the genotypes were analyzed using PCR-restriction fragment length polymorphism and automated sequencing techniques.Results
The *3/*3 thymidylate synthase genotype was associated with a higher response rate (pathological complete remission and microfoci residual tumor; 61 vs. 22% in *2/*2 and *2/*3; P = 0.013). In the multivariate analysis, the *3/*3 thymidylate synthase genotype was also an independent prognostic factor for better survival (P < 0.05).Conclusions
The thymidylate synthase genotype might help to identify patients with stage II/III rectal cancer who could benefit from pre- and postoperative fluorouracil-based chemotherapy. 相似文献47.
Font-Llitjós M Rodríguez-Santiago B Espino M Sillué R Mañas S Gómez L Pérez-Jurado LA Palacín M Nunes V 《European journal of human genetics : EJHG》2009,17(1):71-79
Lysinuric protein intolerance (LPI) is a rare autosomal inherited disease caused by defective cationic aminoacid transport 4F2hc/y(+)LAT-1 at the basolateral membrane of epithelial cells in the intestine and kidney. LPI is a multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. The SLC7A7 gene, which encodes the y(+)LAT-1 protein, is mutated in LPI patients. Mutation analysis of the promoter localized in intron 1 and all exons of the SLC7A7 gene was performed in 11 patients from 9 unrelated LPI families. Point mutation screening was performed by exon direct sequencing and a new multiplex ligation probe amplification (MLPA) assay was set up for large rearrangement analysis. Eleven SLC7A7-specific mutations were identified, seven of them were novel: p.L124P, p.C425R, p.R468X, p.Y274fsX21, c.625+1G>C, DelE4-E11 and DelE6-E11. The novel large deletions originated by the recombination of Alu repeats at introns 3 and 5, respectively, with the same AluY sequence localized at the SLC7A7 3' region. The novel MLPA assay is robust and valuable for LPI molecular diagnosis. Our results suggest that genomic rearrangements of SLC7A7 play a more important role in LPI than has been reported, increasing the detection rate from 5.1 to 21.4%. Moreover, the 3' region AluY repeat could be a recombination hot spot as it is involved in 38% of all SLC7A7 rearranged chromosomes described so far. 相似文献
48.
Laia Rodriguez-Revenga Irene Madrigal Javier Pagonabarraga Mar Xunclà Celia Badenas Jaime Kulisevsky Beatriz Gomez Montserrat Milà 《European journal of human genetics : EJHG》2009,17(10):1359-1362
Within the past few years, there has been a significant change in identifying and characterizing the FMR1 premutation associated phenotypes. The premutation has been associated with elevated FMR1 mRNA levels and slight to moderate reductions in FMRP levels. Furthermore, it has been established that ∼20% of female premutation carriers present primary ovarian insufficiency (POI) and that fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in one-third of all male premutation carriers older than 50 years. Besides POI and FXTAS, new disorders have recently been described among individuals (especially females) with the FMR1 premutation. Those pathologies include thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. However there are few reports related to FXTAS penetrance among female premutation carriers or regarding these disorders recently associated to the FMR1 premutation. Therefore, we have evaluated 398 fragile X syndrome (FXS) families in an attempt to provide an estimation of the premutation associated phenotypes penetrance. Our results show that signs of FXTAS are detected in 16.5% of female premutation carriers and in 45.5% of premutated males older than 50 years. Furthermore, among females with the FMR1 premutation, penetrance of POI, thyroid disease and chronic muscle pain is 18.6, 15.9 and 24.4%, respectively. The knowledge of this data might be useful for accurate genetic counselling as well as for a better characterization of the clinical phenotypes of FMR1 premutation carriers. 相似文献
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