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141.
Xuan Zhao Jiqing Fang Yu Jia Zi Wu Meihui Zhang Mingyu Xia Jinhua Dong 《Molecules (Basel, Switzerland)》2022,27(11)
A series of 1,7-diphenyl-1,4-heptadien-3-ones with various substituents (HO-, CH3O-, CH3-, Cl-) on the phenyl rings were synthesized and evaluated for anti-neuroinflammatory effects in LPS-stimulated BV2 microglia. The pharmacological results showed that the target compounds bearing methoxy groups greatly inhibited LPS-induced NO release, and that the active compounds CU-19 and CU-21 reduced the level of NO, TNF-α, IL-6 and PGE-2, downregulated the expression of COX-2 and iNOS in LPS-stimulated BV2 cells. A study of the mechanism of action revealed that CU-19 and CU-21 inhibited the nuclear translocation of NF-κB and phosphorylation of MAPKs (ERK, JNK, and p38). A preliminary pharmacokinetic study in rats revealed that the pharmacokinetic properties of CU-19 and CU-21 were dramatically ameliorated in comparison with the pharmacokinetic properties of curcumin. 相似文献
142.
Suvarna H. Pagire Haushabhau S. Pagire Kun-Young Park Eun Jung Bae Kwang-eun Kim Minhee Kim Jihyeon Yoon Saravanan Parameswaran Jun-Ho Choi Sungmi Park Jae-Han Jeon Jin Sook Song Myung Ae Bae In-Kyu Lee Hail Kim Jae Myoung Suh Jin Hee Ahn 《Molecules (Basel, Switzerland)》2022,27(11)
Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation. 相似文献
143.
Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases, including Alzheimer''s disease (AD), type II diabetes (T2D), and medullary thyroid carcinoma (MTC). While significant efforts have been made to develop different prevention strategies and preclinical hits for these diseases, conventional design strategies of amyloid inhibitors are mostly limited to either a single prevention mechanism (amyloid cascade vs. microbial infection) or a single amyloid protein (Aβ, hIAPP, or hCT), which has prevented the launch of any successful drug on the market. Here, we propose and demonstrate a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins, human α-defensin 6 (HD-6) and human β-defensin 1 (HBD-1), as multiple-target, dual-function, amyloid inhibitors. Both HD-6 and HBD-1 can cross-seed with three amyloid peptides, Aβ (associated with AD), hIAPP (associated with T2D), and hCT (associated with MTC), to prevent their aggregation towards amyloid fibrils from monomers and oligomers, rescue SH-SY5Y and RIN-m5F cells from amyloid-induced cytotoxicity, and retain their original antimicrobial activity against four common bacterial strains at sub-stoichiometric concentrations. Such sequence-independent anti-amyloid and anti-bacterial functions of intestinal defensins mainly stem from their cross-interactions with amyloid proteins through amyloid-like mimicry of β-sheet associations. In a broader view, this work provides a new out-of-the-box thinking to search and repurpose a huge source of antimicrobial peptides as amyloid inhibitors, allowing the blocking of the two interlinked pathological pathways and bidirectional communication between the central nervous system and intestines via the gut–brain axis associated with neurodegenerative diseases.Amyloid formation and microbial infection are the two common pathological causes of neurogenerative diseases. Here, we proposed a new “anti-amyloid and anti-bacteria” strategy to repurpose two intestinal defensins as multiple-target, dual-function amyloid inhibitors. 相似文献
144.
La2Zr2O7(LZO)过渡层以其独特的物理化学性质越来越受到人们的关注。本文以乙酰丙酮镧和乙酰丙酮锆为前驱盐,丙酸为溶剂配置前驱液,用化学溶液方法(CSD)在具有立方织构的Ni-5at%W基底上制备了LZO过渡层薄膜。研究了前驱液成分、性质以及退火温度对LZO成相以及取向的影响。用常规XRD和X射线四环衍射仪分析了LZO薄膜的相成分和织构。结果显示,在1050℃下退火可以获得强立方织构的LZO薄膜,其中(222)峰的Phi扫描半高宽值为8.95°;(400)峰的Chi扫描半高宽值为6.8°。用高分辨扫描电子显微镜(FE-SEM)观察到LZO薄膜表面均匀致密,没有裂纹和空洞。 相似文献
145.
简要介绍了微波烧结的特点,对 Al2 O3 陶瓷的微波烧结过程进行了介绍和分析,并同常规烧结进行了对比实验,在此基础上得出了一些结论,为陶瓷微波烧结提供了实验依据 相似文献
146.
147.
服务计算系统资源层的目标是满足服务实例的资源分配需求,保证其成功执行而不陷入死锁和活锁.首先将服务资源分配行为形式化为有限状态机;其次提出一种避免死锁和活锁的资源分配算法,它采用并发请求资源的方式,且不需要并发服务实例之间交换消息.仿真实验结果表明,该算法能够避免服务资源分配过程中的死锁和活锁,表现出较高资源分配性能. 相似文献
148.
State feedback controller design of networked control systems 总被引:7,自引:0,他引:7
Dong Yue Qing-Long Han Chen Peng 《Circuits and Systems II: Express Briefs, IEEE Transactions on》2004,51(11):640-644
This paper is concerned with the controller design of networked control systems (NCS). A new model of the NCSs is provided under consideration of both the network-induced delay and the data packet dropout in the transmission. In terms of the given model, a controller design method is proposed based on a delay-dependent approach. The feedback gain of a memoryless controller and the maximum allowable value of the network-induced delay can be derived by solving a set of linear matrix inequalities. Two examples are given to show the effectiveness of our method. 相似文献
149.
加扰CCSK信号具有良好的性能,频谱效率高,信号具有LPI-LPD特性,能够抗多径干扰并具有一定的多址能力;对其信号的自相关特性和频谱特征进行了分析,并针对其信号特征对其信号的抗截获能力进行了探讨;最后对加扰CCSK技术的应用前景进行了展望。 相似文献
150.
(yxl)φ切压电石英谐振器振动模式分析 总被引:1,自引:0,他引:1
从压电方程,动力学方程入手,分析了(yxl)φ切石英谐振器的厚度切变振动,利用自由边界条件及串联与并联谐振时的电学条件,求出了并联谐振频率和串联振频率,讨论了实测频率与频率公式存在一定偏差的原因。 相似文献