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81.
Sopo M Anttila M Sallinen H Tuppurainen L Laurema A Laidinen S Hamalainen K Tuunanen P Koponen JK Kosma VM Heinonen S Alitalo K Yla-Herttuala S 《International journal of cancer. Journal international du cancer》2012,131(10):2394-2401
We compared effects of antiangiogenic gene therapy with a combination of soluble sVEGFR-1, sVEGFR-2 and sVEGFR-3 to chemotherapy with carboplatin and paclitaxel and to antiangiogenic monoclonal anti-VEGF-antibody bevacizumab in an intraperitoneal ovarian cancer xenograft model in mice (n = 80). Gene therapy was also combined with chemotherapy. Therapy was initiated when sizable tumors were confirmed in magnetic resonance imaging (MRI). Adenovirus-mediated gene transfer was performed intravenously (2 × 109 pfu), while chemotherapy and monoclonal anti-VEGF-antibody were dosed intraperitoneally. The study groups were as follows: AdLacZ control (n = 21); combination of AdsVEGFR-1, -2 and -3 (n = 21); combination of AdsVEGFR-1, -2, -3 and paclitaxel (n = 9); bevacizumab (n = 14); paclitaxel (n = 9) and carboplatin (n = 5). Effectiveness was assessed by survival time and surrogate measures such as sequential MRI, immunohistochemistry, microvessel density and tumor growth. Antiangiogenic gene therapy combined with paclitaxel significantly prolonged the mean survival of mice (25 days) compared to the controls (15 days) and all other treatment groups (p = 0.001). Bevacizumab treatment did not have any significant effect on the survival. Tumors of the mice treated by gene therapy were significantly smaller than in the control group (p = 0.021). The mean vascular density and total vascular area were also significantly smaller in the tumors of the gene therapy group (p = 0.01). These results show potential of the antiangiogenic gene therapy to improve efficacy of chemotherapy with paclitaxel and support testing of this approach in a phase I clinical trial for the treatment of ovarian cancer. 相似文献
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83.
Sandbacka M Bruce S Halttunen M Puhakka M Lahermo P Hannula-Jouppi K Lipsanen-Nyman M Kere J Aittomäki K Laivuori H 《Fertility and sterility》2011,95(8):2703-2706
Severe hypomethylation of the H19 imprinted control region (ICR1) in two patients with Silver-Russell syndrome (SRS) who have genital malformations has encouraged us to study DNA methylation in a cohort of 83 patients with Müllerian aplasia (MA). Site-specific methylation analyses of H19 ICR1 by quantitative real-time polymerase chain reaction in 80 clinically well-diagnosed Finnish MA patients showed no association between hypomethylation and the MA phenotype, but studies of the H19 locus in 38 patients showed aberrant methylation in 3/16 studied sites. 相似文献
84.
Tiina‐Riikka M. Pirttil Asla Pitknen Jarkko Tuunanen Risto A. Kauppinen 《Magnetic resonance in medicine》2001,46(5):946-954
The present study was designed to investigate whether T(2)-weighted signal changes obtained by microimaging of paraformaldehyde-fixed brain correlate with the histologically quantified damage in a model of status epilepticus (SE) induced by kainic acid in the rat. Animals were killed at several time points up to 8 weeks after a single intraperitoneal kainate (KA) injection (9 mg/kg). Perfusion-fixed brains were embedded in gelatin for MR microimaging at 9.4T. After the MRI analysis, the gelatin was removed and the brains were cryoprotected and processed for quantitative histology. Severity of neuronal damage and gliosis were assessed from thionin-stained serial sections. Correlative analysis of microimaging and histology data was done in the hippocampus, amygdala, parietal rhinal cortex (PaRH), piriform cortex (Pir), and entorhinal cortex. The relative signal intensities in T(2)-weighted images correlate with the severity of neuronal damage in the matched histological sections (correlation coefficients of 0.752-0.826). Our data show that MR microimaging ex vivo detects the degree of neuronal damage and its anatomical distribution after KA-induced SE, thus providing a useful tool for detecting the dynamics of progressive neuronal damage after prolonged seizures. 相似文献
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86.
Rare missense mutations in RECQL and POLG associate with inherited predisposition to breast cancer 下载免费PDF全文
Anna Tervasmäki Saila Kauppila Hang‐Mao Lee Susanna Koivuluoma Mervi Grip Peeter Karihtala Arja Jukkola‐Vuorinen Arto Mannermaa Robert Winqvist Katri Pylkäs 《International journal of cancer. Journal international du cancer》2018,142(11):2286-2292
Several known breast cancer susceptibility genes with moderate‐to‐high risk alleles encode proteins involved in DNA damage response (DDR). As these explain less than half of the hereditary breast cancer cases, additional predisposing alleles are likely to be discovered. Many of the previous studies utilizing massive parallel sequencing have focused on the protein‐truncating variants, and the role of rare missense mutations has remained poorly addressed. To identify novel susceptibility factors, we have systematically analyzed the data from our parallel sequencing of 796 DDR genes in 189 Northern Finnish hereditary breast cancer patients for rare missense variants, predicted as deleterious. Thirty‐five variants were studied here for the disease association using Finnish breast cancer case (n = 492–2,035) and control (n = 277–1,539) cohorts. As a result, two missense variants in genes involved in DNA replication, RECQL p.I156M and POLG p.L392V, the former involving genomic and the latter mitochondrial DNA replication, showed significant association with risk of breast cancer. Rare RECQL p.I156M allele was observed in breast cancer cases only (6/1,946, 0.3%, p = 0.043), whereas POLG p.L392V was two times more frequent in breast cancer cases (53/2,238, 2.4%) compared to controls (18/1,539, 1.2%, OR = 2.1, 95% CI 1.2–3.5, p = 0.010). Based on the current genetic data, both RECQL p.I156M and POLG p.L392V represent novel breast cancer predisposing alleles. 相似文献
87.
Presenting features and imaging in childhood acute myeloid leukemia with central nervous system involvement 下载免费PDF全文
Susanna Ranta Maarit Palom?ki Mette Levinsen Mervi Taskinen Jonas Abrahamsson Henrik Hasle Kirsi Jahnukainen Mats Heyman Arja Harila‐Saari 《Pediatric blood & cancer》2017,64(12)
Central nervous system (CNS) involvement in childhood acute myeloid leukemia (AML) can manifest as leukemic cells in the cerebrospinal fluid, a solid CNS tumor, or as neurological symptoms. We evaluated the presenting symptoms and neuroimaging findings in 33 of 34 children with AML and CNS involvement at diagnosis in the period 2000–2012 in Sweden, Finland, and Denmark. Imaging was performed in 22 patients, of whom 16 had CNS‐related symptoms. Seven patients, including all but two with facial palsy, had mastoid cell opacification, considered an incidental finding. The frequent involvement of the mastoid bone with facial palsy warrants evaluation in larger series. 相似文献
88.
Capnocytophaga canimorsus: a rare case of conservatively treated prosthetic valve endocarditis 下载免费PDF全文
Päivi Jalava‐Karvinen Juha O. Grönroos Helena Tuunanen Jukka Kemppainen Jarmo Oksi Ulla Hohenthal 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2018,126(5):453-456
We describe a rare case of prosthetic valve endocarditis caused by the canine bacterium Capnocytophaga canimorsus in a male aged 73 years. The diagnosis of infective endocarditis was unequivocal, as it blood cultures were positive for C. canimorsus and vegetations were detected on transesophageal echocardiography; the modified Duke criteria were fulfilled. PET‐CT showed intense 18F‐FDG uptake of the prosthetic valve area. The patient was treated with antibiotics alone (no surgery), and is now on life‐long suppressive antibiotic therapy. To our knowledge, this is the third reported case of prosthetic valve endocarditis caused by C. canimorsus and the first one to have been treated conservatively. 相似文献
89.
Vilppu J Tuominen Sanna Ruotoistenmäki Arttu Viitanen Mervi Jumppanen Jorma Isola 《Breast cancer research : BCR》2010,12(4):R56
Introduction
Accurate assessment of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 is essential in the histopathologic diagnostics of breast cancer. Commercially available image analysis systems are usually bundled with dedicated analysis hardware and, to our knowledge, no easily installable, free software for immunostained slide scoring has been described. In this study, we describe a free, Internet-based web application for quantitative image analysis of ER, PR, and Ki-67 immunohistochemistry in breast cancer tissue sections. 相似文献90.
Elina Siljamäki Laura Raiko Mervi Toriseva Liisa Nissinen Tuomas Näreoja Juha Peltonen Veli-Matti Kähäri Sirkku Peltonen 《Archives of dermatological research》2014,306(2):131-141
Increasing evidence has recognized tight junctions (TJs) as the lower epidermal inside-out diffusion barrier located in granular cell layers of the epidermis. However, little is known about the regulation of TJ components in epidermis. p38 pathway is one of the mitogen-activated protein kinase pathways, which controls cell growth, differentiation, and apoptosis. We have investigated the role of p38 signaling pathway in the regulation of selected desmosomal, adherens and TJ components in human primary keratinocytes during Ca2+-induced differentiation, as well as in cultured squamous cell carcinoma cell lines. p38 signaling pathway was inhibited in cultured keratinocytes and cutaneous squamous cell carcinoma cells using recombinant adenoviruses, small inhibitory RNAs (siRNA) and chemical inhibitors. Expression of intercellular junction proteins was investigated using Western analysis and indirect immunofluorescence (IIF). The results showed that inhibition of p38δ function by siRNA or adenovirally delivered dominant negative mutant led to markedly decreased levels of Zonula occludens-1 (ZO-1) protein in keratinocytes, while the expression of other junctional proteins studied was not altered. Immunolocalization of ZO-1 revealed that intercellular junction areas were depleted from ZO-1. Inhibition of ZO-1 by siRNA silencing did not however result in an altered expression or subcellular localization of other TJ components studied. The expression of ZO-1 in carcinoma cells was also regulated by p38. The results indicate that ZO-1 is regulated by p38δ while the other junction proteins studied are not. Since ZO-1 is an integral component of functional TJs, various pathological processes affecting signaling via p38δ may also interfere with epithelial maturation and the formation and function of TJs. 相似文献