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排序方式: 共有484条查询结果,搜索用时 37 毫秒
1.
Sebastian Reuther Silke Szymczak Annette Raabe Kerstin Borgmann Andreas Ziegler Cordula Petersen Ekkehard Dikomey Ulrike Hoeller 《Strahlentherapie und Onkologie》2015,191(1):59-66
Background and purpose
The aim of this study was to determine the impact of functional single nucleotide polymorphism (SNP) pathways involved in the ROS pathway, DNA repair, or TGFB1 signaling on acute or late normal toxicity as well as individual radiosensitivity.Materials and methods
Patients receiving breast-conserving surgery and radiotherapy were examined either for erythema (n?=?83), fibrosis (n?=?123), or individual radiosensitivity (n?=?123). The 17 SNPs analyzed are involved in the ROS pathway (GSTP1, SOD2, NQO1, NOS3, XDH), DNA repair (XRCC1, XRCC3, XRCC6, ERCC2, LIG4, ATM) or TGFB signaling (SKIL, EP300, APC, AXIN1, TGFB1). Associations with biological and clinical endpoints were studied for single SNPs but especially for combinations of SNPs assuming that a SNP is either beneficial or deleterious and needs to be weighted.Results
With one exception, no significant association was seen between a single SNP and the three endpoints studied. No significant associations were also observed when applying a multi-SNP model assuming that each SNP was deleterious. In contrast, significant associations were obtained when SNPs were suggested to be either beneficial or deleterious. These associations increased, when each SNP was weighted individually. Detailed analysis revealed that both erythema and individual radiosensitivity especially depend on SNPs affecting DNA repair and TGFB1 signaling, while SNPs in ROS pathway were of minor importance.Conclusion
Functional pathways of SNPs may be used to form a risk score allowing to predict acute and late radiation-induced toxicity but also to unravel the underlying biological mechanisms.2.
Melanie F. Weingart Jacquelyn J. Roth Marianne Hutt-Cabezas Tracy M. Busse Harpreet Kaur Antoinette Price Rachael Maynard Jeffrey Rubens Isabella Taylor Xing-gang Mao Jingying Xu Yasumichi Kuwahara Sariah J. Allen Anat Erdreich-Epstein Bernard E. Weissman Brent A. Orr Charles G. Eberhart Jaclyn A. Biegel Eric H. Raabe 《Oncotarget》2015,6(5):3165-3177
Atypical teratoid rhabdoid tumor (AT/RT) is among the most fatal of all pediatric brain tumors. Aside from loss of function mutations in the SMARCB1 (BAF47/INI1/SNF5) chromatin remodeling gene, little is known of other molecular drivers of AT/RT. LIN28A and LIN28B are stem cell factors that regulate thousands of RNAs and are expressed in aggressive cancers. We identified high-levels of LIN28A and LIN28B in AT/RT primary tumors and cell lines, with corresponding low levels of the LIN28-regulated microRNAs of the let-7 family. Knockdown of LIN28A by lentiviral shRNA in the AT/RT cell lines CHLA-06-ATRT and BT37 inhibited growth, cell proliferation and colony formation and induced apoptosis. Suppression of LIN28A in orthotopic xenograft models led to a more than doubling of median survival compared to empty vector controls (48 vs 115 days). LIN28A knockdown led to increased expression of let-7b and let-7g microRNAs and a down-regulation of KRAS mRNA. AT/RT primary tumors expressed increased mitogen activated protein (MAP) kinase pathway activity, and the MEK inhibitor selumetinib (AZD6244) decreased AT/RT growth and increased apoptosis. These data implicate LIN28/RAS/MAP kinase as key drivers of AT/RT tumorigenesis and indicate that targeting this pathway may be a therapeutic option in this aggressive pediatric malignancy. 相似文献
3.
A. Raabe H.-P. Beck-Bornholdt A. Krüll J. O. Zieron W. Alberti 《International journal of radiation biology》2013,89(9):947-954
Purpose : The aim was to investigate the influence of pulmonary metastases of the rhabdomyosarcoma R1H on the radiation response of the lung of the WAG/Rij rat. Material and methods : Three groups of animals were investigated: metastases-free animals treated with fractionated irradiation of the lungs; metastases-bearing animals receiving no irradiation; and metastases-bearing animals treated with fractionated irradiation initiated 14, 21 or 28 days after induction of pulmonary metastases of the R1H-tumour by i.v. injection of viable tumour cells. Metastases were thus treated at various well-defined sizes. Total doses of 20-60Gy were applied in fractions of 2 Gy within 11 days. Complication rate and survival time were used as endpoints. Results : About 2 months after onset of irradiation treatment, animals had to be sacrificed because of severe respiratory distress either caused by irradiation-induced lung damage (median 57 days, range 36-77 days), or because of development of lung metastases (65, 20-160 days). A decrease of the ED 50 (dose required to induce lethal lung damage in 50% of irradiated animals) was determined for metastases-bearing animals. This effect increased with metastatic volume. Conclusions : The results suggest that the presence of tumours in the lung decreased the lung tolerance to radiation. This effect can hardly be explained by a reduction in functional lung volume by metastatic volume. 相似文献
4.
Knockout of the abetalipoproteinemia gene in mice: Reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes 总被引:12,自引:0,他引:12 下载免费PDF全文
Martin Raabe Laura M. Flynn Constance H. Zlot Jinny S. Wong Murielle M. Vniant Robert L. Hamilton Stephen G. Young 《Proceedings of the National Academy of Sciences of the United States of America》1998,95(15):8686-8691
Abetalipoproteinemia, an inherited human disease characterized by a near-complete absence of the apolipoprotein (apo) B-containing lipoproteins in the plasma, is caused by mutations in the gene for microsomal triglyceride transfer protein (MTP). We used gene targeting to knock out the mouse MTP gene (Mttp). In heterozygous knockout mice (Mttp+/− ), the MTP mRNA, protein, and activity levels were reduced by 50%, in both liver and intestine. Compared with control mice (Mttp+/+), chow-fed Mttp+/− mice had reduced plasma levels of low-density lipoprotein cholesterol and had a 28% reduction in plasma apoB100 levels. On a high-fat diet, the Mttp+/− mice exhibited a marked reduction in total plasma cholesterol levels, compared with those in Mttp+/+ mice. Both the livers of adult Mttp+/− mice and the visceral endoderm of the yolk sacs from Mttp+/− embryos manifested an accumulation of cytosolic fat. All homozygous embryos (Mttp−/−) died during embryonic development. In the visceral endoderm of Mttp−/− yolk sacs, lipoprotein synthesis was virtually absent, and there was a marked accumulation of cytosolic fat droplets. In summary, half-normal MTP levels do not support normal levels of lipoprotein synthesis and secretion, and a complete deficiency of MTP causes lethal developmental abnormalities, perhaps because of an impaired capacity of the yolk sac to export lipids to the developing embryo. 相似文献
5.
Schahnaz Alloussi Gerd Mürtz Reinhard Braun Ulrich Gerhardt Martina Heinrich Eva Hellmis Werner Horn Daniela Marschall‐Kehrel Kurt Niklas Michael Raabe Thomas Rößler Beatrix Seibt Stefan Siemer Daniela Schultz‐Lampel Heiko Walter Burkhard Wiedeking Saladin Alloussi Paul Bock Gerhard Strugala Helmut Madersbacher 《BJU international》2010,106(4):550-556
Study Type – Therapy (observational cohort)Level of Evidence 2b
OBJECTIVE
To compare, in a retrospective observational cohort study, the efficacy, tolerability and safety of propiverine and oxybutynin in children with urge incontinence (UI) due to overactive bladder.PATIENTS AND METHODS
Medical records were scrutinized for children with UI. As a primary efficacy outcome variable the achievement of continence after treatment with variable doses of propiverine or oxybutynin was assessed. Weekly UI episodes and daily voiding frequency were evaluated as secondary efficacy outcomes. Tolerability was evaluated by the rate of adverse events, adverse drug reactions caused by antimuscarinics and premature treatment termination.RESULTS
At 16 study centres, 621 children aged 5–14 years with UI due to overactive bladder were enrolled. After anticholinergic treatment (437 propiverine, 184 oxybutynin) continence was achieved in 61.6% and 58.7% of the patients after 186 and 259 days, respectively. There were clinically relevant improvements in voiding frequency across treatment groups. Daily doses of propiverine were markedly below the recommendations (0.54 vs 0.8 mg/kg body weight), daily doses of oxybutynin were according to the recommendations (0.31 vs 0.2–0.4 mg/kg body weight) at treatment initiation. There was a significantly more favourable tolerability to propiverine than oxybutynin for the overall rate of adverse events (3.9% vs 16.3%, odds ratio 4.813), adverse drug reactions caused by propiverine or oxybutynin (2.8% vs 9.2%) and premature treatment termination due to adverse drug reactions (1.6% vs 4.4%).CONCLUSION
Propiverine and oxybutynin are effective in children with UI due to overactive bladder. Sufficient treatment periods of at least 2, preferably 3–4, months are the crucial factors for a successful treatment. The tolerability profile of propiverine is better than for oxybutynin. 相似文献6.
We evaluated 50 patients who suffered a single myocardial infarction with graded electrocardiographic stress testing, 201thallium myocardial perfusion imaging and coronary angiography to assess the role of noninvasive indices as predictors of single versus multivessel coronary artery disease. Multivessel involvement was defined angiographically as the presence of two or more major coronary arteries with at least a 70% intraluminal diameter narrowing. Multivessel disease was defined scintigraphically as the presence of stress and/or redistribution perfusion defects in the distribution of more than one coronary artery. The results of stress electrocardiography were not useful in differentiating patients with single (9/16 positive) versus multivessel (22/34 positive) disease. The degree of exercise-induced ST-segment depression was also not helpful. Stress 201thallium imaging did offer limited additional information with correct predictions of multivessel disease in 21 of 26 patients. Predictions of single-vessel disease were accurate in 11 of 24 patients. Eleven of these 13 incorrect predictions of single-vessel disease were due to the relative insensitivity of the thallium stress image to perceive defect in the anterior wall when the left anterior descending artery had significant obstruction at catheterization. Further refinements of stress perfusion imaging are needed before this method can be used to reliably separate patients with single and multivessel disease after myocardial infarction. 相似文献
7.
Poupon RE Bonnand AM Queneau PE Trépo C Zarski JPí Vetter D Raabe JJ Thieffin G Larrey D Grangé JD Capron JP Serfaty L Chrétien Y St Marc Girardin MF Mathiex-Fortunet H Zafrani ES Guéchot J Beuers U Paumgartner G Poupon R 《Scandinavian journal of gastroenterology》2000,35(6):642-649
BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids. 相似文献
8.
A. Raabe D. Van De Ville M. Leutenegger A. Szelnyi E. Hattingen R. Gerlach V. Seifert C. Hauger A. Lopez R. Leitgeb M. Unser E.J. Martin-Williams T. Lasser 《NeuroImage》2009,44(4):1284-1289
The identification and accurate location of centers of brain activity are vital both in neuro-surgery and brain research. This study aimed to provide a non-invasive, non-contact, accurate, rapid and user-friendly means of producing functional images intraoperatively. To this end a full field Laser Doppler imager was developed and integrated within the surgical microscope and perfusion images of the cortical surface were acquired during awake surgery whilst the patient performed a predetermined task. The regions of brain activity showed a clear signal (10–20% with respect to the baseline) related to the stimulation protocol which lead to intraoperative functional brain maps of strong statistical significance and which correlate well with the preoperative fMRI and intraoperative cortical electro-stimulation. These initial results achieved with a prototype device and wavelet based regressor analysis (the hemodynamic response function being derived from MRI applications) demonstrate the feasibility of LDI as an appropriate technique for intraoperative functional brain imaging. 相似文献
9.
Andreas C. Raabe Oliver Billker Henri J. Vial Kai Wengelnik 《Molecular and biochemical parasitology》2009,168(2):172-176
Targeting the crucial step of Plasmodium transition from vertebrate host to mosquito vector is a promising approach to eliminate malaria. Uptake by the mosquito activates gametocytes within seconds, and in the case of male (micro) gametocytes leads to rapid DNA replication and the release of eight flagellated gametes. We developed a sensitive assay to monitor P. berghei microgametocyte activation based on [3H]hypoxanthine incorporation into DNA. Optimal pH range and xanthurenic acid concentrations for gametocyte activation were established and the kinetics of DNA replication investigated. Significance of the method was confirmed using P. berghei mutants and the assay was applied to analyse the effect of protease inhibitors, which revealed differences regarding their inhibitory action. The developed method thus appears suitable for reproducible determination of microgametocyte activation, medium-throughput drug screenings and deeper investigation of early blocks in gametogenesis and will facilitate the analysis of compounds for transmission blocking activities. 相似文献
10.
Philippe Schucht Sonja Knittel Johannes Slotboom Kathleen Seidel Michael Murek Astrid Jilch Andreas Raabe Jürgen Beck 《Acta neurochirurgica》2014,156(2):305-312