全文获取类型
收费全文 | 1281篇 |
免费 | 135篇 |
国内免费 | 55篇 |
专业分类
化学 | 1069篇 |
力学 | 13篇 |
综合类 | 39篇 |
数学 | 128篇 |
物理学 | 222篇 |
出版年
2024年 | 7篇 |
2023年 | 41篇 |
2022年 | 138篇 |
2021年 | 166篇 |
2020年 | 115篇 |
2019年 | 45篇 |
2018年 | 39篇 |
2017年 | 48篇 |
2016年 | 67篇 |
2015年 | 66篇 |
2014年 | 64篇 |
2013年 | 81篇 |
2012年 | 53篇 |
2011年 | 66篇 |
2010年 | 35篇 |
2009年 | 43篇 |
2008年 | 43篇 |
2007年 | 48篇 |
2006年 | 32篇 |
2005年 | 29篇 |
2004年 | 27篇 |
2003年 | 23篇 |
2002年 | 13篇 |
2001年 | 17篇 |
2000年 | 32篇 |
1999年 | 20篇 |
1998年 | 21篇 |
1997年 | 30篇 |
1996年 | 15篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 7篇 |
1990年 | 3篇 |
1988年 | 1篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1976年 | 1篇 |
排序方式: 共有1471条查询结果,搜索用时 15 毫秒
71.
Alba L. Montoya Eileni R. Gil Emily L. Heydemann Igor L. Estevao Bianca E. Luna Cameron C. Ellis Sohan R. Jankuru Belkisyol Alarcn de Noya Oscar Noya Maria Paola Zago Igor C. Almeida Katja Michael 《Molecules (Basel, Switzerland)》2022,27(2)
Chagas disease (CD) can be accurately diagnosed by detecting Trypanosoma cruzi in patients’ blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method’s limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages. Nevertheless, these stages also abundantly express cell surface glycosylphosphatidylinositol (GPI)-anchored glycoproteins and glycoinositolphospholipids (GIPLs) bearing nonreducing terminal β-galactofuranosyl (β-Galf) residues, which are equally foreign to humans and, therefore, highly immunogenic. Here we report that CCD patients’ sera react specifically with synthetic β-Galf-containing glycans. We took a reversed immunoglycomics approach that entailed: (a) Synthesis of T. cruzi GIPL-derived Galfβ1,3Manpα-(CH2)3SH (glycan G29SH) and Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα-(CH2)3SH (glycan G32SH); and (b) preparation of neoglycoproteins NGP29b and NGP32b, and their evaluation in a chemiluminescent immunoassay. Receiver-operating characteristic analysis revealed that NGP32b can distinguish CCD sera from sera of healthy individuals with 85.3% sensitivity and 100% specificity. This suggests that Galfβ1,3Manpα1,2-[Galfβ1,3]Manpα is an immunodominant glycotope and that NGP32b could potentially be used as a novel CCD biomarker. 相似文献
72.
Rosalba Leuci Leonardo Brunetti Antonio Laghezza Luca Piemontese Antonio Carrieri Leonardo Pisani Paolo Tortorella Marco Catto Fulvio Loiodice 《Molecules (Basel, Switzerland)》2022,27(3)
A new series of aryloxyacetic acids was prepared and tested as peroxisome proliferator-activated receptors (PPARs) agonists and fatty acid amide hydrolase (FAAH) inhibitors. Some compounds exhibited an interesting dual activity that has been recently proposed as a new potential therapeutic strategy for the treatment of Alzheimer’s disease (AD). AD is a multifactorial pathology, hence multi-target agents are currently one of the main lines of research for the therapy and prevention of this disease. Given that cholinesterases represent one of the most common targets of recent research, we decided to also evaluate the effects of our compounds on the inhibition of these specific enzymes. Interestingly, two of these compounds, (S)-5 and 6, showed moderate activity against acetylcholinesterase (AChE) and even some activity, although at high concentration, against Aβ peptide aggregation, thus demonstrating, in agreement with the preliminary dockings carried out on the different targets, the feasibility of a simultaneous multi-target activity towards PPARs, FAAH, and AChE. As far as we know, these are the first examples of molecules endowed with this pharmacological profile that might represent a promising line of research for the identification of novel candidates for the treatment of AD. 相似文献
73.
Biophysical computational models are complementary to experiments and theories, providing powerful tools for the study of neurological diseases. The focus of this review is the dynamic modeling and control strategies of Parkinson's disease (PD). In previous studies, the development of parkinsonian network dynamics modeling has made great progress. Modeling mainly focuses on the cortex-thalamus-basal ganglia (CTBG) circuit and its sub-circuits, which helps to explore the dynamic behavior of the parkinsonian network, such as synchronization. Deep brain stimulation (DBS) is an effective strategy for the treatment of PD. At present, many studies are based on the side effects of the DBS. However, the translation from modeling results to clinical disease mitigation therapy still faces huge challenges. Here, we introduce the progress of DBS improvement. Its specific purpose is to develop novel DBS treatment methods, optimize the treatment effect of DBS for each patient, and focus on the study in closed-loop DBS. Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment. 相似文献
74.
75.
Parkinson’s disease (PD) is characterized by the decrease of dopamine (DA) production and release in the substantia nigra and striatum regions of the brain. Transcranial ultrasound has been exploited recently for neuromodulation of the brain in a number of fields. We have stimulated DA release in PC12 cells using low-intensity continuous ultrasound (0.1 W/cm2 − 0.3 W/cm2, 1 MHz), 12 h after exposure at 0.2 W/cm2, 40 s, the amount of DA content eventually increased 78.5% (p = 0.004). After 10-day ultrasonic treatment (0.3 W/cm2, 5 min/d), the DA content in the striatum of PD mice model restored to 81.07% of the control (vs 43.42% in the untreated PD mice model). In addition to this the locomotion activity was restored to the normal level after treatment. We suggest that the low intensity ultrasound-induced DA release can be attributed to a combination of neuron regeneration and improved membrane permeability produced by the mechanical force of ultrasound. Our study indicates that the application of transcranial ultrasound applied below FDA limits, could provide a candidate for relatively safe and noninvasive PD therapy through an amplification of DA levels and the stimulation of dopaminergic neuron regeneration without contrast agents. 相似文献
76.
77.
Over the last few years, breath analysis for the routine monitoring of metabolic disorders has attracted a considerable amount of scientific interest, especially since breath sampling is a non-invasive technique, totally painless and agreeable to patients. The investigation of human breath samples with various analytical methods has shown a correlation between the concentration patterns of volatile organic compounds (VOCs) and the occurrence of certain diseases. It has been demonstrated that modern analytical instruments allow the determination of many compounds found in human breath both in normal and anomalous concentrations. The composition of exhaled breath in patients with, for example, lung cancer, inflammatory lung disease, hepatic or renal dysfunction and diabetes contains valuable information. Furthermore, the detection and quantification of oxidative stress, and its monitoring during surgery based on composition of exhaled breath, have made considerable progress. This paper gives an overview of the analytical techniques used for sample collection, preconcentration and analysis of human breath composition. The diagnostic potential of different disease-marking substances in human breath for a selection of diseases and the clinical applications of breath analysis are discussed. 相似文献
78.
心脑血管疾病与微量元素研究进展 总被引:3,自引:2,他引:3
心脑血管疾病发病日益增多的原因之一是机体缺乏人体必需微量元素,目前报道硒、锗、锌、钴、铜、锰、铬、钼、钒、镍等与心脑血管疾病有密切关系。用微量元素调控防治心脑血管疾病,目前是国内外研究的新课题,其目的是降低心脑血管疾病的死亡率和发病率,促进人类健康长寿。 相似文献
79.
Hongyu Zhang Changlong Hao Aihua Qu Maozhong Sun Liguang Xu Chuanlai Xu Hua Kuang 《Angewandte Chemie (International ed. in English)》2020,59(18):7131-7138
The accumulation and deposition of β‐amyloid (Aβ) plaques in the brain is considered a potential pathogenic mechanism underlying Alzheimer's disease (AD). Chiral l/d ‐FexCuySe nanoparticles (NPs) were fabricated that interfer with the self‐assembly of Aβ42 monomers and trigger the Aβ42 fibrils in dense structures to become looser monomers under 808 nm near‐infrared (NIR) illumination. d ‐FexCuySe NPs have a much higher affinity for Aβ42 fibrils than l ‐FexCuySe NPs and chiral Cu2?xSe NPs. The chiral FexCuySe NPs also generate more reactive oxygen species (ROS) than chiral Cu2?xSe NPs under NIR‐light irradiation. In living MN9D cells, d ‐NPs attenuate the adhesion of Aβ42 to membranes and neuron loss after NIR treatment within 10 min without the photothermal effect. In‐vivo experiments showed that d ‐FexCuySe NPs provide an efficient protection against neuronal damage induced by the deposition of Aβ42 and alleviate symptoms in a mouse model of AD, leading to the recovery of cognitive competence. 相似文献
80.
Yujie Wang Rong Wen Dongdong Liu Chen Zhang Zhuo A. Wang Yuguang Du 《Molecules (Basel, Switzerland)》2021,26(8)
Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects. 相似文献