全文获取类型
收费全文 | 120篇 |
免费 | 14篇 |
国内免费 | 5篇 |
专业分类
化学工业 | 103篇 |
金属工艺 | 3篇 |
机械仪表 | 1篇 |
建筑科学 | 3篇 |
轻工业 | 7篇 |
无线电 | 3篇 |
一般工业技术 | 3篇 |
冶金工业 | 13篇 |
自动化技术 | 3篇 |
出版年
2023年 | 4篇 |
2022年 | 20篇 |
2021年 | 13篇 |
2020年 | 8篇 |
2019年 | 7篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 10篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 4篇 |
2012年 | 5篇 |
2011年 | 9篇 |
2010年 | 13篇 |
2009年 | 12篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2001年 | 2篇 |
1999年 | 1篇 |
1996年 | 1篇 |
排序方式: 共有139条查询结果,搜索用时 10 毫秒
131.
Modulation of Retinoic Acid Receptor Subtypes by 5‐ and 8‐Substituted (Naphthalen‐2‐yl)‐based Arotinoids 下载免费PDF全文
132.
Dopamine (DA) in the medial prefrontal cortex (PFC) can modulate the short-term retention of information and other executive functions. The present study examined whether administration of a DA D? agonist into the PFC could have differential effects on memory retrieval in circumstances in which memory was either excellent or poor. Separate groups of rats were trained on a delayed version of the radial maze task. On the test day, the delay between the phases was either 30 min or 12 hr. Infusions of the D? receptor agonist SKF 81297 (0.05, 0.10, or 0.20 Ag/0.5 P1) into the PFC before the test phase improved memory retrieval after a 12-hr delay but disrupted performance after a 30-min delay. These data suggest that D? receptor activity can exert differential effects over PFC function, depending on the strength of the memory trace. When memory is decremented by an extended delay, activation of PFC DA D? receptors by an agonist can improve cognitive function. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
133.
Giordano Traini Ane Ruiz‐de‐Angulo Juan Bautista Blanco‐Canosa Kepa Zamacola Bascarn Antonio Molinaro Alba Silipo David Escors Juan C. Mareque‐Rivas 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(4)
Despite the tremendous potential of Toll‐like receptor 4 (TLR4) agonists in vaccines, their efficacy as monotherapy to treat cancer has been limited. Only some lipopolysaccharides (LPS) isolated from particular bacterial strains or structures like monophosphoryl lipid A (MPLA) derived from lipooligosaccharide (LOS), avoid toxic overactivation of innate immune responses while retaining adequate immunogenicity to act as adjuvants. Here, different LOS structures are incorporated into nanoparticle‐filled phospholipid micelles for efficient vaccine delivery and more potent cancer immunotherapy. The structurally unique LOS of the plant pathogen Xcc is incorporated into phospholipid micelles encapsulating iron oxide nanoparticles, producing stable pathogen‐mimicking nanostructures suitable for targeting antigen presenting cells in the lymph nodes. The antigen is conjugated via a hydrazone bond, enabling rapid, easy‐to‐monitor and high‐yield antigen ligation at low concentrations. The protective effect of these constructs is investigated against a highly aggressive model for tumor immunotherapy. The results show that the nanovaccines lead to a higher‐level antigen‐specific cytotoxic T lymphocyte (CTL) effector and memory responses, which when combined with abrogation of the immunosuppressive programmed death‐ligand 1 (PD‐L1), provide 100% long‐term protection against repeated tumor challenge. This nanovaccine platform in combination with checkpoint inhibition of PD‐L1 represents a promising approach to improve the cancer immunotherapy of TLR4 agonists. 相似文献
134.
Claassen Daniel O.; van den Wildenberg Wery P. M.; Ridderinkhof K. Richard; Jessup Charles K.; Harrison Madaline B.; Wooten G. Frederick; Wylie Scott A. 《Canadian Metallurgical Quarterly》2011,125(4):492
Risk-taking behavior is characterized by pursuit of reward in spite of potential negative consequences. Dopamine neurotransmission along the mesocorticolimbic pathway is a potential modulator of risk behavior. In patients with Parkinson's disease (PD), impulse control disorder (ICD) can result from dopaminergic medication use, particularly dopamine agonists (DAA). Behaviors associated with ICD include hypersexuality as well as compulsive gambling, shopping, and eating, and these behaviors are potentially linked to alterations to risk processing. Using the Balloon Analogue Risk Task, we assessed the role of agonist therapy on risk-taking behavior in PD patients with (n = 22) and without (n = 19) active ICD symptoms. Patients performed the task both “on” and “off” DAA. DAA increased risk-taking in PD patients with active ICD symptoms, but it did not affect risk behavior of PD controls. DAA dose was also important in explaining risk behavior. Both groups similarly reduced their risk-taking in high compared to low risk conditions and following the occurrence of a negative consequence, suggesting that ICD patients do not necessarily differ in their abilities to process and adjust to some aspects of negative consequences. Our findings suggest dopaminergic augmentation of risk-taking behavior as a potential contributing mechanism for the emergence of ICD in PD patients. (PsycINFO Database Record (c) 2011 APA, all rights reserved) 相似文献
135.
136.
Ayumu Sato Dr. Yoshiyuki Fukase Mitsunori Kono Dr. Atsuko Ochida Tsuneo Oda Dr. Yusuke Sasaki Naoki Ishii Dr. Yoshihide Tomata Dr. Shoji Fukumoto Dr. Yumi N. Imai Keiko Uga Dr. Akira Shibata Dr. Masashi Yamasaki Hideyuki Nakagawa Mikio Shirasaki Dr. Robert Skene Dr. Isaac Hoffman Dr. Bi-Ching Sang Dr. Gyorgy Snell Dr. Junya Shirai Dr. Satoshi Yamamoto 《ChemMedChem》2019,14(22):1917-1932
Retinoic-acid-related orphan receptor γt (RORγt) inverse agonists could be used for the treatment of autoimmune diseases. Previously, we reported a novel quinazolinedione 1 a with a flexible linear linker as a novel RORγt inverse agonist. A U-shaped conformation in the complex structure of 1 a with RORγt protein was confirmed. Further improvement of the pharmacokinetic (PK) profiles was required because of the low drug exposure in mice upon oral administration (mouse AUC of 1 a : 27 ng ⋅ h ⋅ mL−1 at 1 mg ⋅ kg−1, p.o.). To improve the PK profiles, conformationally constrained U-shaped scaffolds were investigated. As a result, morpholine analogues with improved PK profiles and high potency were successfully identified. The substituent at the N1 position of the quinazoline moiety was also modified, leading to an enhancement of reporter activity. Consequently, compound 43 (N2-(3-chloro-4-cyanophenyl)-N4-(3-(cyclopropylmethyl)-1-isopropyl-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-6-yl)morpholine-2,4-dicarboxamide) exhibited improved drug exposure (mouse AUC: 1289 ng ⋅ h ⋅ mL−1 at 1 mg ⋅ kg−1, p.o.). In addition, suppression of IL-17A gene expression by IL-23 stimulation in a mouse pharmacodynamics model was observed for 43 . The conformation of 43 with RORγt protein was also confirmed as U-shape by X-ray co-crystal structure analysis. The key interaction that boosts potency is also discussed. 相似文献
137.
For thousands of years mu opioid agonists such as morphine have been utilized for their analgesic properties. Today, morphine and related compounds are still used as a first line therapy in the treatment of moderate to severe pain. However, despite the clear benefits of mu agonists in pain management, severe side effects such as dependence and respiratory depression are associated with use of these drugs. To date, there are only two approved mu opioid antagonists for use in the treatment of these adverse effects, that is, naloxone and naltrexone. However, many other clinical and therapeutic areas have been linked to mu opioid receptor antagonism. These include treatment of opioid induced pruritus of the skin, obesity, and Parkinson-induced tardive dyskinesia. Currently there are two compounds, N-methylnaltrexone and alvimopan, under FDA review as possible treatments for opioid induced bowel dysfunction and postoperative ileus. These compounds are of special interest as they are peripherally restricted. This attribute enables treatment of peripheral side effects induced by opioid agonists without reversal of the centrally mediated analgesia of the agonist. In this article we discuss the structural classes of mu opioid antagonists, their potential clinical applications, and review the relevant patents of the last ten years. 相似文献
138.
Xiangling Cui Yongli Xie Min Zhang Jieke Gao Xujun Zhou Dr. Jiwei Ding Dr. Shan Cen Dr. Jinming Zhou 《ChemMedChem》2022,17(11):e202100719
Given the emerging pivotal roles of stimulator of interferon genes (STING) in host pathogen defense and immune-oncology, STING is regarded as a promising target for drug development. Cyclic dinucleotides (CDNs) are the first-generation STING agonists. However, their poor metabolic stability and membrane permeability limits their therapeutic application. In contrast, small-molecule STING agonists show superior properties such as molecular weight, polar character, and delivery diversity. The quest for a potent small-molecular agonist of human STING remains ongoing. In our study, through an IRF/IFN pathway-targeted cell-based screen of a natural products library, we identified a small-molecular STING agonist, Ziyuglycoside II, termed ST12, with potent stimulation of the IRF/IFN and NF-κB pathways. Furthermore, its binding to the C-terminal domain of human STING, detected by bio-layer interferometry, indicates that ST12 is a human STING agonist. Further Tanimoto similarity analysis with existing small-molecule STING agonists indicates that ST12 is a lead compound with a novel core structure for the further optimization. 相似文献
139.
Stefan Löber Dr. Nuska Tschammer Dr. Harald Hübner Dr. Maria Rosaria Melis Prof. Dr. Antonio Argiolas Prof. Dr. Peter Gmeiner Prof. Dr. 《ChemMedChem》2009,4(3):325-328
Blue makes it happen : The non‐uniform charge distribution of the blue colored azulene framework is highly suitable for the bioisosteric replacement of bicyclic heteroarene moieties. Showing an analogous binding mode as heterocyclic dopamine D4 receptor‐selective lead compounds, the induction of penile erection in rats over a greater range of doses indicates a putative advantage of the rationally developed azulene derivative 2 b over apomorphine.