全文获取类型
收费全文 | 281篇 |
免费 | 12篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 5篇 |
基础医学 | 58篇 |
口腔科学 | 4篇 |
临床医学 | 34篇 |
内科学 | 20篇 |
神经病学 | 81篇 |
特种医学 | 4篇 |
外科学 | 35篇 |
预防医学 | 12篇 |
眼科学 | 1篇 |
药学 | 4篇 |
肿瘤学 | 35篇 |
出版年
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2016年 | 10篇 |
2015年 | 11篇 |
2014年 | 7篇 |
2013年 | 10篇 |
2012年 | 26篇 |
2011年 | 15篇 |
2010年 | 8篇 |
2009年 | 6篇 |
2008年 | 9篇 |
2007年 | 13篇 |
2006年 | 12篇 |
2005年 | 11篇 |
2004年 | 12篇 |
2003年 | 6篇 |
2002年 | 10篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 10篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 6篇 |
1991年 | 11篇 |
1990年 | 4篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有294条查询结果,搜索用时 15 毫秒
101.
Pfister S Remke M Toedt G Werft W Benner A Mendrzyk F Wittmann A Devens F von Hoff K Rutkowski S Kulozik A Radlwimmer B Scheurlen W Lichter P Korshunov A 《Genes, chromosomes & cancer》2007,46(9):839-851
Supratentorial primitive neuroectodermal tumors (stPNETs) and medulloblastomas have long been thought to arise from a common cell type in the subventricular germinal matrix. Because of the infrequent occurrence of stPNETs, little is known about their genetic background. Here, we performed a genome-wide screening for DNA copy-number aberrations in 10 supratentorial PNETs using array-based comparative genomic hybridization (array-CGH). Comparing our findings with data from a previous array-CGH study on 47 medulloblastomas, we identified differences in the frequency of copy-number losses at chromosome regions 1p12-22.1 and 9p, and gains at 19p, all of them more frequently occurring in stPNETs. In contrast to previous reports, we detected chromosome 17 aberrations by array-CGH in 2/10 stPNETs. To validate our findings obtained by array-CGH, we analyzed the loci of interest by fluorescence in situ hybridization in an independent set of 11 stPNETs and found deletions of 9p21 in 5/11 tumors of the second set, three of them being homozygous. All 9p21 deletions were associated with loss of CDKN2A protein expression. Altogether, CDKN2A deletions were detected in 7/21 stPNETs including four homozygous deletions, whereas such deletions were only found in 4/112 medulloblastomas, all of these being heterozygous (P < 0.001). Gains of 19p (14% vs. 0% in medulloblastomas, P = 0.02) were found to be significantly more frequent in stPNETs, whereas gains of 17q (14% vs. 45% in medulloblastomas, P = 0.02) were confirmed to be more frequent in medulloblastomas. These data further support the hypothesis of two different tumor entities of embryonal neuroepithelial tumors with characteristic genetic aberrations. (c) 2007 Wiley-Liss, Inc. 相似文献
102.
Benedikt Wiestler David Capper Martin Sill David T. W. Jones Volker Hovestadt Dominik Sturm Christian Koelsche Anna Bertoni Leonille Schweizer Andrey Korshunov Elisa K. Weiß Maximilian G. Schliesser Alexander Radbruch Christel Herold-Mende Patrick Roth Andreas Unterberg Christian Hartmann Torsten Pietsch Guido Reifenberger Peter Lichter Bernhard Radlwimmer Michael Platten Stefan M. Pfister Andreas von Deimling Michael Weller Wolfgang Wick 《Acta neuropathologica》2014,128(4):561-571
The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMPpos (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMPneg (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMPneg glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMPpos tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMPpos tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMPneg anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort. 相似文献
103.
Ul'in VK Korshunov DV Borodulin AI Kaspranskiĭ RR Khomenchuk AM Gernet MV Kaspranskiĭ RR Firsov SIu 《Aviakosmicheskaia i ekologicheskaia meditsina》2011,45(3):60-63
Functional testing of the bioreactor for stirring culture in microgravity was performed during the microgravity episodes aboard research airplane Il-76 following the Kepler parabolic flight path. The attempt to produce the gas vortex stirring effect in a given liquid volume was a failure. Nonetheless, the stirrer ventilator is capable to agitate liquid acting as a mechanical stirrer. 相似文献
104.
Lorena V Baroni Lakshmikirupa Sundaresan Ayala Heled Hallie Coltin Kristian W Pajtler Tong Lin Thomas E Merchant Roger McLendon Claudia Faria Molly Buntine Christine L White Stefan M Pfister Mark R Gilbert Terri S Armstrong Eric Bouffet Sachin Kumar Michael D Taylor Kenneth D Aldape David W Ellison Nicholas G Gottardo Marcel Kool Andrey Korshunov Jordan R Hansford Vijay Ramaswamy 《Neuro-oncology》2021,23(8):1360
BackgroundWithin PF-EPN-A, 1q gain is a marker of poor prognosis, however, it is unclear if within PF-EPN-A additional cytogenetic events exist which can refine risk stratification.MethodsFive independent non-overlapping cohorts of PF-EPN-A were analyzed applying genome-wide methylation arrays for chromosomal and clinical variables predictive of survival.ResultsAcross all cohorts, 663 PF-EPN-A were identified. The most common broad copy number event was 1q gain (18.9%), followed by 6q loss (8.6%), 9p gain (6.5%), and 22q loss (6.8%). Within 1q gain tumors, there was significant enrichment for 6q loss (17.7%), 10q loss (16.9%), and 16q loss (15.3%). The 5-year progression-free survival (PFS) was strikingly worse in those patients with 6q loss, with a 5-year PFS of 50% (95% CI 45%-55%) for balanced tumors, compared with 32% (95% CI 24%-44%) for 1q gain only, 7.3% (95% CI 2.0%-27%) for 6q loss only and 0 for both 1q gain and 6q loss (P = 1.65 × 10−13). After accounting for treatment, 6q loss remained the most significant independent predictor of survival in PF-EPN-A but is not in PF-EPN-B. Distant relapses were more common in 1q gain irrespective of 6q loss. RNA sequencing comparing 6q loss to 6q balanced PF-EPN-A suggests that 6q loss forms a biologically distinct group.ConclusionsWe have identified an ultra high-risk PF-EPN-A ependymoma subgroup, which can be reliably ascertained using cytogenetic markers in routine clinical use. A change in treatment paradigm is urgently needed for this particular subset of PF-EPN-A where novel therapies should be prioritized for upfront therapy. 相似文献
105.
Ryan SL Schwalbe EC Cole M Lu Y Lusher ME Megahed H O'Toole K Nicholson SL Bognar L Garami M Hauser P Korshunov A Pfister SM Williamson D Taylor RE Ellison DW Bailey S Clifford SC 《Acta neuropathologica》2012,123(4):501-513
The MYC oncogenes are the most commonly amplified loci in medulloblastoma, and have previously been proposed as biomarkers of adverse disease prognosis by us and others. Here, we report focussed and comprehensive investigations of MYCC, MYCN and MYCL in an extensive medulloblastoma cohort (n?=?292), aimed to define more precisely their biological significance and optimal clinical application to direct improved disease risk-stratification and individualisation of therapy. MYCC and MYCN expression elevations were multifactorial, associated with high-risk (gene amplification, large-cell/anaplastic pathology (LCA)) and favourable-risk (WNT/SHH molecular subgroups) disease features. Highly variable cellular gene amplification patterns underlay overall MYC copy number elevations observed in tumour biopsies; we used these alternative measures together to define quantitative methodologies and thresholds for amplification detection in routinely collected tumour material. MYCC and MYCN amplification, but not gain, each had independent prognostic significance in non-infants (≥3.0-16.0?years), but MYCC conferred a greater hazard to survival than MYCN when considered across this treatment group. MYCN's weaker group-wide survival relationship may be explained by its pleiotropic behaviour between clinical disease-risk groups; MYCN predicted poor prognosis in clinical high-risk (metastatic (M+) or LCA), but not standard-risk, patients. Extending these findings, survival decreased in proportion to the total number of independently significant high-risk features present (LCA, M+ or MYCC/MYCN amplification). This cumulative-risk model defines a patient group characterised by ≥2 independent risk-factors and an extremely poor prognosis (<15% survival), which can be identified straightforwardly using the reported MYC amplification detection methodologies alongside clinical assessments, enabling targeting for novel/intensified therapies in future clinical studies. 相似文献
106.
Korshunov VA 《Journal of neuroscience methods》2012,206(1):15-22
The design of a miniature multichannel preamplifier for extracellular recordings of single unit activity in freely moving and swimming small animals is presented. The advantages of this design include perfect protection of the critical components and electric contacts from water. Thus, neuronal activity and EEG may be recorded differentially in any kinds of behavioral tasks including swimming in Morris water maze. Recordings are stable even if an animal is diving and swimming under the water surface. The reusable dismountable base can adopt different types of chronically implanted fine wire electrodes and movable arrays. Electrodes may be implanted to any desired depth. The assembly weight is less than 240 mg. Thus, the construction is light enough even for mice. This work is the first successful attempt for multichannel recording of neuronal activity in mice performing spatial task in Morris water maze. 相似文献
107.
108.
It is suggested that information on new stimuli from the neocortex is transmitted to the hippocampus, where temporal traces
persist in the form of mosaics of modified synapses. During sleep, populations of neurons storing these traces are reactivated
and return the information required for consolidation of a permanent memory trace to the neocortex. A possible mechanism for
the reactivation of “trained” hippocampal neurons during memory consolidation consists of the reverberation of excitation
in the neuron circuits linking the hippocampus and entorhinal cortex. Our studies in rats included recording of responses
in hippocampal field CA1 to stimulation of Schaffer collaterals with potentiated synapses during waking and sleep. During
deep sleep, discharges of field CA1 neurons were followed by waves of excitation which passed through the entorhinal cortex
and reached the hippocampus and dentate gyrus via fibers of the perforant path, evoking neuron discharges in the latter. Repeated
neuron discharges in field CA1 occurred on interaction of the early excitation wave returning directly via perforant path
fibers and the late wave returning via Schaffer collaterals, not via the trisynaptic path via the dentate gyrus and hippocampal
field CA3 but probably via field CA2. 相似文献
109.
110.
It has been suggested that the effects of angiotensin II type 1 receptor (AT1R) blockers are in part because of angiotensin II type 2 receptor (AT2R) signaling. Interactions between the AT2R and kinins modulate cardiovascular function. Because AT2R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT1R blocker valsartan and the ACE inhibitor benazepril require AT2R signaling through the bradykinin 1 and 2 receptors (B1R and B2R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (n=16): valsartan, valsartan+PD123319 (AT2R inhibitor), valsartan+des-arg9-[Leu8]-bradykinin (B1R inhibitor), valsartan+HOE140 (B2R inhibitor), benazepril, benazepril+HOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT2R, B1R, or B2R in the presence of valsartan prevented the reduction seen with valsartan alone. B2R blockade inhibited the effect of benazepril. Injury increased AT1R, AT2R, B1R, and B2R expression. Treatment with valsartan but not benazepril significantly increased intima AT2R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT2R, B1R, and B2R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT2R, B1R, and B2R. Results suggest that AT2R expression and increased cGMP represent a molecular mechanism that differentiates AT1R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril. 相似文献