全文获取类型
收费全文 | 628篇 |
免费 | 46篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 5篇 |
妇产科学 | 16篇 |
基础医学 | 75篇 |
口腔科学 | 9篇 |
临床医学 | 65篇 |
内科学 | 170篇 |
皮肤病学 | 4篇 |
神经病学 | 72篇 |
特种医学 | 29篇 |
外科学 | 76篇 |
综合类 | 2篇 |
预防医学 | 58篇 |
眼科学 | 2篇 |
药学 | 49篇 |
肿瘤学 | 38篇 |
出版年
2023年 | 8篇 |
2022年 | 11篇 |
2021年 | 19篇 |
2020年 | 13篇 |
2019年 | 11篇 |
2018年 | 26篇 |
2017年 | 16篇 |
2016年 | 14篇 |
2015年 | 31篇 |
2014年 | 28篇 |
2013年 | 39篇 |
2012年 | 63篇 |
2011年 | 66篇 |
2010年 | 36篇 |
2009年 | 28篇 |
2008年 | 43篇 |
2007年 | 41篇 |
2006年 | 40篇 |
2005年 | 27篇 |
2004年 | 30篇 |
2003年 | 29篇 |
2002年 | 28篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1959年 | 1篇 |
1922年 | 2篇 |
排序方式: 共有675条查询结果,搜索用时 15 毫秒
631.
Changes in GABAA receptor α1 subunit gene expression occur in the globus pallidus and substantia nigra pars reticulata following lesions of the nigrostriatal tract. To determine whether these changes are translated at the protein level, we performed quantitative autoradiography with the α1 selective ligand, [3H]zolpidem, and the non-selective benzodiazepine site ligand, [3H]Ro 15-1788. Binding of both [3H]zolpidem and [3H]Ro 15-1788 was significantly increased in the substantia nigra pars reticulata (13.5±4.1 and 26.3±2.9%, respectively) and significantly reduced in the globus pallidus (20.9±0.8 and 18.3±1.3%, respectively). These changes in α1 subunit protein expression may help to compensate for the pathological changes in GABAergic activity that occur after striatal dopamine depletion. 相似文献
632.
Zeng Z O'Brien JA Lemaire W O'Malley SS Miller PJ Zhao Z Wallace MA Raab C Lindsley CW Sur C Williams DL 《Nuclear medicine and biology》2008,35(3):315-325
INTRODUCTION: In an effort to develop agents to test the NMDA hypofunction hypothesis of schizophrenia, benchmark compounds from a program to discover potent, selective, competitive glycine transporter 1 (GlyT1) inhibitors were radiolabeled in order to further study the detailed pharmacology of these inhibitors and the distribution of GlyT1 in brain. We here report the in vitro characterization of [35S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl)benzamide ([35S]ACPPB), a radiotracer developed from a potent and selective non-sarcosine-derived GlyT1 inhibitor, its use in autoradiographic studies to localize (S)-2-amino-6-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl)benzamide (ACPPB) binding sites in rat and rhesus brain and for in vivo occupancy assays of competitive GlyT1 inhibitors. METHODS: Functional potencies of unlabeled compounds were characterized by [14C]glycine uptake into JAR (human placental choriocarcinoma) cells and synaptosomes. Radioligand binding studies were performed with tissue homogenates. Autoradiographic studies were performed on tissue slices. RESULTS: ACPPB is a potent (Kd=1.9 nM), selective, GlyT1 inhibitor that, when radiolabeled with [35S], is a well-behaved radioligand with low nondisplaceable binding. Autoradiographic studies of rat and rhesus brain slices with this ligand showed that specific binding sites were plentiful and nonhomogeneously distributed, with high levels of binding in the brainstem, cerebellar white matter, thalamus, cortical white matter and spinal cord gray matter. In vivo studies demonstrate displaceable binding of [35S]ACPPB in rat brain tissues following iv administration of this radioligand. CONCLUSIONS: This is the first report of detailed anatomical localization of GlyT1 using direct radioligand binding, and the first demonstration that an in vivo occupancy assay is feasible, suggesting that it may also be feasible to develop positron emission tomography tracers for GlyT1. 相似文献
633.
634.
In vivo imaging of brain lesions with [(11)C]CLINME, a new PET radioligand of peripheral benzodiazepine receptors 总被引:2,自引:0,他引:2
Boutin H Chauveau F Thominiaux C Kuhnast B Grégoire MC Jan S Trebossen R Dollé F Tavitian B Mattner F Katsifis A 《Glia》2007,55(14):1459-1468
The peripheral benzodiazepine receptor (PBR) is expressed by microglial cells in many neuropathologies involving neuroinflammation. PK11195, the reference compound for PBR, is used for positron emission tomography (PET) imaging but has a limited capacity to quantify PBR expression. Here we describe the new PBR ligand CLINME as an alternative to PK11195. In vitro and in vivo imaging properties of [(11)C]CLINME were studied in a rat model of local acute neuroinflammation, and compared with the reference compound [(11)C]PK11195, using autoradiography and PET imaging. Immunohistochemistry study was performed to validate the imaging data. [(11)C]CLINME exhibited a higher contrast between the PBR-expressing lesion site and the intact side of the same rat brain than [(11)C]PK11195 (2.14 +/- 0.09 vs. 1.62 +/- 0.05 fold increase, respectively). The difference was due to a lower uptake for [(11)C]CLINME than for [(11)C]PK11195 in the non-inflammatory part of the brain in which PBR was not expressed, while uptake levels in the lesion were similar for both tracers. Tracer localization correlated well with that of activated microglial cells, demonstrated by immunohistochemistry and PBR expression detected by autoradiography. Modeling using the simplified tissue reference model showed that R(1) was similar for both ligands (R(1) approximately 1), with [(11)C]CLINME exhibiting a higher binding potential than [(11)C]PK11195 (1.07 +/- 0.30 vs. 0.66 +/- 0.15). The results show that [(11)C]CLINME performs better than [(11)C]PK11195 in this model. Further studies of this new compound should be carried out to better define its capacity to overcome the limitations of [(11)C]PK11195 for PBR PET imaging. 相似文献
635.
Harousseau JL Attal M Leleu X Troncy J Pegourie B Stoppa AM Hulin C Benboubker L Fuzibet JG Renaud M Moreau P Avet-Loiseau H 《Haematologica》2006,91(11):1498-1505
636.
The new EU legislations for chemicals (Registration, Evaluation and Authorization of Chemicals, REACH) and cosmetics (Seventh Amendment) stimulate the acceptance of in vitro and in silico approaches to test chemicals for their potential to cause reproductive effects. In the current study seven compounds with known in vivo developmental effects were tested in the embryonic stem cell test (EST). The EST correctly classified 5-fluorouracil, methotrexate, retinoic acid, 2-ethoxyacetic acid and 2-methoxyacetic acid for their in vivo embryotoxic potential. The toxicity of 2-methoxyethanol and 2-ethoxyethanol was underestimated due to a lack of metabolic capacity in the EST. This study further investigated the possibility to use in silico techniques to extrapolate in vitro effect concentrations determined in the EST to in vivo exposure levels. This approach was evaluated by comparing in silico predicted in vivo effect levels with effect levels measured in rodents. The in vivo effect levels of 2-methoxyethanol, 2-ethoxyethanol, methotrexate and retinoic acid were correctly predicted with in silico modelling. Contrary, in vivo embryotoxicity of 5-fluorouracil was overestimated following this approach. It is concluded that a combination of in vitro and in silico techniques appears to be a promising alternative test method for risk assessment of embryotoxic compounds. 相似文献
637.
Magne C Astésano C Lacheret-Dujour A Morel M Alter K Besson M 《Journal of cognitive neuroscience》2005,17(5):740-756
Highlighting relevant information in a discourse context is a major aim of spoken language communication. Prosodic cues such as focal prominences are used to fulfill this aim through the pragmatic function of prosody. To determine whether listeners make on-line use of focal prominences to build coherent representations of the informational structure of the utterances, we used the brain event-related potential (ERP) method. Short dialogues composed of a question and an answer were presented auditorily. The design of the experiment allowed us to examine precisely the time course of the processing of prosodic patterns of sentence-medial or -final words in the answer. These patterns were either congruous or incongruous with regard to the pragmatic context introduced by the question. Furthermore, the ERP effects were compared for words with or without focal prominences. Results showed that pragmatically congruous and incongruous prosodic patterns elicit clear differences in the ERPs, which were largely modulated in latency and polarity by their position within the answer. By showing that prosodic patterns are processed on-line by listeners in order to understand the informational structure of the message, the present results demonstrate the psychobiological validity of the pragmatic concept of focus, expressed via prosodic cues. Moreover, the functional significance of the positive-going effects found sentence medially and negative-going effects found sentence finally is discussed. Whereas the former may reflect the processing of surprising and task-relevant prosodic patterns, the latter may reflect the integration problems encountered in extracting the overall informational structure of the sentence. 相似文献
638.
Rabodonirina M Vanhems P Couray-Targe S Gillibert RP Ganne C Nizard N Colin C Fabry J Touraine JL van Melle G Nahimana A Francioli P Hauser PM 《Emerging infectious diseases》2004,10(10):1766-1773
Ten Pneumocystis jirovecii pneumonia (PCP) cases were diagnosed in renal transplant recipients (RTRs) during a 3-year period. Nosocomial transmission from HIV-positive patients with PCP was suspected because these patients shared the same hospital building, were not isolated, and were receiving suboptimal anti-PCP prophylaxis or none. P. jirovecii organisms were typed with the multitarget polymerase chain reaction-single-strand conformation polymorphism method. Among the 45 patients with PCP hospitalized during the 3-year period, 8 RTRs and 6 HIV-infected patients may have encountered at least 1 patient with active PCP within the 3 months before the diagnosis of their own PCP episode. In six instances (five RTRs, one HIV-infected patient), the patients harbored the same P. jirovecii molecular type as that found in the encountered PCP patients. The data suggest that part of the PCP cases observed in this building, particularly those observed in RTRs, were related to nosocomial interhuman transmission. 相似文献
639.
640.
Blot F Edé C Nitenberg GM 《The New England journal of medicine》2002,347(25):2080-1; author reply 2080-1