全文获取类型
收费全文 | 1828篇 |
免费 | 746篇 |
国内免费 | 179篇 |
专业分类
化学 | 537篇 |
晶体学 | 30篇 |
力学 | 186篇 |
综合类 | 37篇 |
数学 | 130篇 |
物理学 | 1833篇 |
出版年
2024年 | 6篇 |
2023年 | 15篇 |
2022年 | 39篇 |
2021年 | 66篇 |
2020年 | 83篇 |
2019年 | 47篇 |
2018年 | 59篇 |
2017年 | 123篇 |
2016年 | 92篇 |
2015年 | 110篇 |
2014年 | 165篇 |
2013年 | 177篇 |
2012年 | 147篇 |
2011年 | 158篇 |
2010年 | 129篇 |
2009年 | 131篇 |
2008年 | 150篇 |
2007年 | 142篇 |
2006年 | 127篇 |
2005年 | 101篇 |
2004年 | 95篇 |
2003年 | 78篇 |
2002年 | 75篇 |
2001年 | 72篇 |
2000年 | 57篇 |
1999年 | 54篇 |
1998年 | 51篇 |
1997年 | 33篇 |
1996年 | 30篇 |
1995年 | 26篇 |
1994年 | 10篇 |
1993年 | 17篇 |
1992年 | 24篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 7篇 |
1988年 | 8篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1971年 | 1篇 |
1957年 | 2篇 |
排序方式: 共有2753条查询结果,搜索用时 20 毫秒
91.
Weidong Liu 《固体与材料科学评论》2015,40(3):137-163
Metallic glass (MG) is amorphous and has some outstanding properties such as ultrahigh strength, superior elasticity, and excellent thermo-plasticity. However, as MG is relatively new to the metal family, the relationship between its physical properties and amorphous structure is still unclear. This article aims to provide an insightful discussion through a comprehensive review about the investigations in the past few decades on the scientific mechanisms of this class of material. The discussion of the paper will include the following key aspects: (1) the formation mechanism of an amorphous structure through glass transition, (2) the structural characterization and models, (3) the micromechanics of plastic event and shear band, and (4) the correlation between the amorphous structure and its mechanical properties. 相似文献
92.
《Current Applied Physics》2015,15(3):326-329
The effect of cooling rate on the thermal stability and soft magnetic properties of [(Fe0.5Co0.5)0.75B0.2Si0.05]100-xNbx (x = 5, 6, 7, 8 at. %) system was investigated. The alloys were produced into the form of ribbon and cylindrical rod by melt-spinning and injection casting, respectively. Their structure, thermal, mechanical and soft magnetic properties were investigated by x-ray diffraction, differential scanning calorimetry, universal testing machine and vibrating sample magnetometer, respectively. All of the alloys were identified as fully amorphous by X-ray diffraction. It turned out that the rod samples had exceptionally high saturation fields reaching 3.0 kOe, which is key properties for sensor application. Also, among these Fe,Co-based samples, the Fe35.25 Co35.25 B18.8 Si4.70 Nb6 ribbon exhibits the highest saturation magnetization with 142.1 emu/g. 相似文献
93.
《Current Applied Physics》2015,15(2):59-63
We have synthesized an efficient Cu2ZnSn(SxSe1−x)4 (CZTSSe) absorbers by using single-step rapid thermal sulfo-selenization process of sputtered stack metallic precursor (Zn/Sn/Cu) films. The structural and morphological studies confirm that the suitability of the rapid thermal sulfo-selenization process for the synthesis of a CZTSSe absorber without any secondary phases with large grains. The annealing atmosphere with a mixed-chalcogen source enhances the grain growth of the CZTSSe absorber as compared with pure Cu2ZnSnS4 (CZTS) and Cu2ZnSnSe4 (CZTSe) absorbers. The CZTSSe thin film solar cell shows the best conversion efficiency of ∼7%. 相似文献
94.
A.V. Veselovsky M.S. Zharkova V.V. Poroikov M.C. Nicklaus 《SAR and QSAR in environmental research》2014,25(6):457-471
Protein–protein interactions (PPI) are involved in most of the essential processes that occur in organisms. In recent years, PPI have become the object of increasing attention in drug discovery, particularly for anti-HIV drugs. Although the use of combinations of existing drugs, termed highly active antiretroviral therapy (HAART), has revolutionized the treatment of HIV/AIDS, problems with these agents, such as the rapid emergence of drug-resistant HIV-1 mutants and serious adverse effects, have highlighted the need for further discovery of new drugs and new targets. Numerous investigations have shown that PPI play a key role in the virus’s life cycle and that blocking or modulating them has a significant therapeutic potential. Here we summarize the recent progress in computer-aided design of PPI inhibitors, mainly focusing on the selection of the drug targets (HIV enzymes and virus entry machinery) and the utilization of peptides and small molecules to prevent a variety of protein–protein interactions (viral–viral or viral–host) that play a vital role in the progression of HIV infection. 相似文献
95.
Redesigning the DNA‐Targeted Chromophore in Platinum–Acridine Anticancer Agents: A Structure–Activity Relationship Study 下载免费PDF全文
Dr. Amanda J. Pickard Dr. Fang Liu Thomas F. Bartenstein Laura G. Haines Dr. Keith E. Levine Prof. Gregory L. Kucera Prof. Ulrich Bierbach 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(49):16174-16187
Platinum–acridine hybrid agents show low‐nanomolar potency in chemoresistant non‐small cell lung cancer (NSCLC), but high systemic toxicity in vivo. To reduce the promiscuous genotoxicity of these agents and improve their pharmacological properties, a modular build–click–screen approach was used to evaluate a small library of twenty hybrid agents containing truncated and extended chromophores of varying basicities. Selected derivatives were resynthesized and tested in five NSCLC cell lines representing large cell, squamous cell, and adenocarcinomas. 7‐Aminobenz[c]acridine was identified as a promising scaffold in a hybrid agent ( P1–B1 ) that maintained submicromolar activity in several of the DNA‐repair proficient and p53‐mutant cancer models, while showing improved tolerability in mice by 32‐fold compared to the parent platinum–acridine ( P1–A1 ). The distribution and DNA/RNA adduct levels produced by the acridine‐ and benz[c]acridine‐based analogues in NCI‐H460 cells (confocal microscopy, ICP‐MS), and their ability to bind G‐quadruplex forming DNA sequences (CD spectroscopy, HR‐ESMS) were studied. P1–B1 emerges as a less genotoxic, more tolerable, and potentially more target‐selective hybrid agent than P1–A1 . 相似文献
96.
Probing the Anticancer Mechanism of (−)‐Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation 下载免费PDF全文
Dr. Chao Li Ting Dong Qiang Li Prof. Dr. Xiaoguang Lei 《Angewandte Chemie (International ed. in English)》2014,53(45):12111-12115
Herein, we report an efficient approach for exploring the novel anticancer mechanism of (?)‐ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by pretarget imaging revealed that PPARγ, a nucleus receptor, was a functional cellular target of ainsliatrimer A. We also confirmed that the anticancer activity of ainsliatrimer A was caused by the activation of PPARγ. 相似文献
97.
Meilian Zhao Feng Yang Prof. Ying Xue Prof. Dan Xiao Prof. Yong Guo 《Chemphyschem》2014,15(1):157-164
A comprehensive first‐principles theoretical study of the electronic properties and half‐metallic nature of zigzag edge‐oxidized graphene quantum dots (GQDs) is carried out by using density functional theory (DFT) with the screened exchange hybrid functional of Heyd, Scuseria and Ernzerhof (HSE06). The oxidation schemes include ‐OH, ‐COOH and ‐COO groups. We identify oxidized GQDs whose opposite spins are localized at the two zigzag edges in an antiferromagnetic‐type configuration, showing a spin‐polarized ground state. Oxidized GQDs are more stable than the corresponding fully hydrogenated GQDs. The partially hydroxylated and carboxylated GQDs with the same size exhibit half‐metallic state under almost the same electric‐field intensity whereas fully oxidized GQDs behave as spin‐selective semiconductors. The electric‐field intensity inducing the half metal increases with the length of the partially oxidized GQDs, ranging from M=4 to 7. 相似文献
98.
冠状病毒是一类广泛存在且对人及家畜具有严重危害的病原体,其中于2003年全球爆发的严重急性呼吸综合征病毒(SARS-CoV)以及2012年被发现并传播的中东呼吸综合征病毒(MERS-CoV)给人们的生命健康以及全球经济造成了严重威胁以及重大损失,特别是2019年末爆发的新型冠状病毒(SARS-CoV-2),截至目前为止已经造成了几百万的感染病例以及几十万人的死亡。可以看出,冠状病毒具有较高的传播性以及较高的致死率,时刻威胁着人们的健康安全,但是针对冠状病毒的感染目前还没有批准上市的有效药物,也没有用于预防的疫苗。本文围绕目前关于冠状病毒的潜在成药性靶点,详细介绍了针对这些靶点的具有代表性的抑制剂的结构设计及其化学合成方法,以期为目前抗冠状病毒药物的研发提供一些参考。 相似文献
99.
Isabel V. L. Wilkinson Kelly J. Perkins Hannah Dugdale Lee Moir Aini Vuorinen Maria Chatzopoulou Sarah E. Squire Sebastian Monecke Alexander Lomow Marcus Geese Philip D. Charles Peter Burch Jonathan M. Tinsley Graham M. Wynne Stephen G. Davies Francis X. Wilson Fraydoon Rastinejad Shabaz Mohammed Kay E. Davies Angela J. Russell 《Angewandte Chemie (International ed. in English)》2020,59(6):2420-2428
Duchenne muscular dystrophy (DMD) is a fatal muscle‐wasting disease arising from mutations in the dystrophin gene. Upregulation of utrophin to compensate for the missing dystrophin offers a potential therapy independent of patient genotype. The first‐in‐class utrophin modulator ezutromid/SMT C1100 was developed from a phenotypic screen through to a Phase 2 clinical trial. Promising efficacy and evidence of target engagement was observed in DMD patients after 24 weeks of treatment, however trial endpoints were not met after 48 weeks. The objective of this study was to understand the mechanism of action of ezutromid which could explain the lack of sustained efficacy and help development of new generations of utrophin modulators. Using chemical proteomics and phenotypic profiling we show that the aryl hydrocarbon receptor (AhR) is a target of ezutromid. Several lines of evidence demonstrate that ezutromid binds AhR with an apparent KD of 50 nm and behaves as an AhR antagonist. Furthermore, other reported AhR antagonists also upregulate utrophin, showing that this pathway, which is currently being explored in other clinical applications including oncology and rheumatoid arthritis, could also be exploited in future DMD therapies. 相似文献
100.
The statin drug Simvastatin is a HMG-CoA reductase inhibitor that has been widely used to lower blood lipid. However, the drug is clinically observed to reposition a significant suppressing potency on glioblastoma (GBM) by unexpectedly targeting diverse kinase pathways involved in GBM tumorigensis. Here, an inverse screening strategy is described to discover potential kinase targets of Simvastatin. Various human protein kinases implicated in GBM are enriched to define a druggable kinome; the binding behavior of Simvastatin to the kinome is profiled systematically via an integrative computational approach, from which most kinases have only low or moderate binding potency to Simvastatin, while only few are identified as promising kinase hits. It is revealed that Simvastatin can potentially interact with certain known targets or key regulators of GBM such as ErbB, c-Src and FGFR signaling pathways, but exhibit low affinity to the well-established GBM target of PI3K/Akt/mTOR pathway. Further assays determine that Simvastatin can inhibit kinase hits EGFR, MET, SRC and HER2 at nanomolar level, which are comparable with those of cognate kinase inhibitors. Structural analyses reveal that the sophisticated T790 M gatekeeper mutation can considerably reduce Simvastatin sensitivity to EGFR by inducing the ligand change between different binding modes. 相似文献