全文获取类型
收费全文 | 34871篇 |
免费 | 5999篇 |
国内免费 | 4650篇 |
专业分类
化学 | 25945篇 |
晶体学 | 648篇 |
力学 | 1926篇 |
综合类 | 362篇 |
数学 | 3931篇 |
物理学 | 12708篇 |
出版年
2024年 | 96篇 |
2023年 | 614篇 |
2022年 | 1078篇 |
2021年 | 1165篇 |
2020年 | 1373篇 |
2019年 | 1400篇 |
2018年 | 1152篇 |
2017年 | 1112篇 |
2016年 | 1604篇 |
2015年 | 1710篇 |
2014年 | 1882篇 |
2013年 | 2608篇 |
2012年 | 3198篇 |
2011年 | 3127篇 |
2010年 | 2332篇 |
2009年 | 2301篇 |
2008年 | 2625篇 |
2007年 | 2217篇 |
2006年 | 2153篇 |
2005年 | 1961篇 |
2004年 | 1530篇 |
2003年 | 1212篇 |
2002年 | 1253篇 |
2001年 | 983篇 |
2000年 | 828篇 |
1999年 | 711篇 |
1998年 | 458篇 |
1997年 | 348篇 |
1996年 | 373篇 |
1995年 | 324篇 |
1994年 | 303篇 |
1993年 | 251篇 |
1992年 | 178篇 |
1991年 | 182篇 |
1990年 | 151篇 |
1989年 | 111篇 |
1988年 | 106篇 |
1987年 | 68篇 |
1986年 | 68篇 |
1985年 | 76篇 |
1984年 | 55篇 |
1983年 | 33篇 |
1982年 | 28篇 |
1981年 | 36篇 |
1980年 | 21篇 |
1979年 | 20篇 |
1978年 | 10篇 |
1977年 | 11篇 |
1976年 | 12篇 |
1975年 | 14篇 |
排序方式: 共有10000条查询结果,搜索用时 437 毫秒
991.
Han H Langley DR Rangan A Hurley LH 《Journal of the American Chemical Society》2001,123(37):8902-8913
G-quadruplex DNA presents a potential target for the design and development of novel anticancer drugs. Because G-quadruplex DNA exhibits structural polymorphism, different G-quadruplex typologies may be associated with different cellular processes. Therefore, to achieve therapeutic selectivity using G-quadruplexes as targets for drug design, it will be necessary to differentiate between different types of G-quadruplexes using G-quadruplex-interactive agents. In this study, we compare the interactions of three cationic porphyrins, TMPyP2, TMPyP3, and TMPyP4, with parallel and antiparallel types of G-quadruplexes using gel mobility shift experiments and a helicase assay. Gel mobility shift experiments indicate that TMPyP3 specifically promotes the formation of parallel G-quadruplex structures. A G-quadruplex helicase unwinding assay reveals that the three porphyrins vary dramatically in their abilities to prevent the unwinding of both the parallel tetrameric G-quadruplex and the antiparallel hairpin dimer G-quadruplex DNA by yeast Sgs1 helicase (Sgs1p). For the parallel G-quadruplex, TMPyP3 has the strongest inhibitory effect on Sgs1p, followed by TMPyP4, but the reverse is true for the antiparallel G-quadruplex. TMPyP2 does not appear to have any effect on the helicase-catalyzed unwinding of either type of G-quadruplex. Photocleavage experiments were carried out to investigate the binding modes of all three porphyrins with parallel G-quadruplexes. The results reveal that TMPyP3 and TMPyP4 appear to bind to parallel G-quadruplex structures through external stacking at the ends rather than through intercalation between the G-tetrads. Since intercalation between G-tetrads has been previously proposed as an alternative binding mode for TMPyP4 to G-quadruplexes, this mode of binding, versus that determined by a photocleavage assay described here (external stacking), was subjected to molecular dynamics calculations to identify the relative stabilities of the complexes and the factors that contribute to these differences. The DeltaG(o) for the external binding mode was found to be driven by DeltaH(o) with a small unfavorable TDeltaS(o) term. The DeltaG(o) for the intercalation binding model was driven by a large TDeltaS(o) term and complemented by a small DeltaH(o) term. One of the main stabilizing components of the external binding model is the energy of solvation, which favors the external model over the intercalation model by -67.94 kcal/mol. Finally, we propose that intercalative binding, although less favored than external binding, may occur, but because of the nature of the intercalative binding, it is invisible to the photocleavage assay. This study provides the first experimental insight into how selectivity might be achieved for different G-quadruplexes by using structural variants within a single group of G-quadruplex-interactive drugs. 相似文献
992.
PrCl3-BaCl2-LiCl三元体系相图的研究 总被引:2,自引:0,他引:2
本文借助于DTA与X射线结构分析研究了PrCl_3-BaCl_2-LiCl三元体系相同。发现本体系内有对应于PrCl_2、α-BaCl_2、β-BaCl_2、LiCl和Ba_2PrCl_3的五个液相面、六条二次结晶线、一个三元低共熔点E(72.1wt%PrCl_3,2.8wt%BaCl_2,25.1wt%LiCl;441℃)和三元转熔点P(62.5wt%PrCl_3,12.5wt%BaCl_2,25.0wt%LiCi;490℃)。同时发现有一固相下形成的不稳定化合物Y(430℃分解)。 相似文献
993.
994.
Masatoshi Taniguchi Ken-ichi SuzumuraKoji Nagai Tomihisa KawasakiTetsu Saito Jun TakasakiKen-ichi Suzuki Shigeo FujitaShin-ichi Tsukamoto 《Tetrahedron》2003,59(25):4533-4538
The isolation and structure elucidation of YM-254890, a novel Gq/11 inhibitor from Chromobacterium sp. QS3666, is described. The gross structure was determined by one- and two-dimensional NMR studies and mass spectrometry. YM-254890 is a cyclic depsipeptide containing uncommon amino acids; β-hydroxyleucine (two residues), N,O-dimethylthreonine and N-methyldehydroalanine. YM-254890 exists as a mixture of two conformers in a variety of NMR solvents, and the distinction between major and minor conformers appears to lie in the geometry of the amide bond between 3-phenyllactic acid and N-methyldehydroalanine. The absolute stereochemistery was elucidated by Marfey's analysis and chiral HPLC analysis of the acid hydrolysate of YM-254890. 相似文献
995.
ShiGuoSUN XiaoJunPENG MingWenFAN YongQianXU LeiSHI LiChengSU 《中国化学快报》2004,15(8):965-968
Two novel rhenium(I) 2, 2′-bipyridyl complexes, [(4,4′-di-COOEt-bipy) Re(CO)3 (NCCH3)PF6] and [(4,4′-di-COOEt-bipy) Re (CO)3 (NCS)], a model complex [(4,4′-di-COOEt-bipy) Re (CO)3 (pyridine)PF6], were synthesized. Their ground state electronic spectra and emission spectra were measured in acetonitrile. The MLCT absorption maximum of the complex exhibited a considerable red shift as the ligand changed from pyridine to CNCH3, or SCN. 相似文献
996.
Synthesis of poly(thiocarbonate)s from the copolymerization of epoxides and carbon disulfide (CS2) remains a tough challenge, due to inevitable oxygen‐sulfur atom scrambling process. In this work, we utilized the oxygen‐sulfur exchange reaction (O‐S ER) to synthesize a random copolymer with monothiocarbonate and trithiocarbonate units from CS2 and phenyl glycidyl ether (PGE) via metal‐free Lewis pairs. The copolymers contained monothiocarbonate and trithiocarbonate units of which the molar fraction could be tuned by varying either the types of Lewis pairs or the reaction temperature. Keeping track on the intermediate provided an insight in the process of O‐S ER and thus gave a hint to control the product structure. Production and consumption of phenyl thioglycidyl ether was the key process to regulate the chain structure. Remarkably, the oxygen atoms of PGE could be excluded out of the chain, resulting in the nearly complete production of poly(trithiocarbonate)s. Correspondingly, the refractive index of this kind of copolymer could be regulated in a wide range of 1.73—1.79 (at 590 nm). 相似文献
997.
Top7 is a de novo designed protein with atomic level accuracy and shows a folded structure not found in nature. Previous studies showed that the folding of Top7 is not cooperative and involves various folding intermediate states. In addition, various fragments of Top7 were found to fold on their own in isolation. These features displayed by Top7 are distinct from those of naturally occurring proteins of a similar size and suggest a rough folding energy landscape. However, it remains unknown if and how the intra-polypeptide chain interactions among the neighboring sequences of Top7 affect the folding of these Top7 fragments. Here we used single-molecule optical tweezers to investigate the folding–unfolding pathways of full length Top7 as well as its C-terminal fragment (CFr) in different sequence environments. Our results showed that the mechanical folding of Top7 involves an intermediate state that likely involves non-native interactions/structure. More importantly, we found that the folding of CFr is entirely dependent upon its sequence context in which it is located. When in isolation, CFr indeed folds into a cooperative structure showing near-equilibrium unfolding–folding transitions at ∼6.5 pN in OT experiments. However, CFr loses its autonomous cooperative folding ability and displays a folding pathway that is dependent on its interactions with its neighboring sequence/structure. This context-dependent folding dynamics and pathway of CFr are distinct from those of naturally occurring proteins and highlight the critical importance of intra-chain interactions in shaping the overall energy landscape and the folding pathway of Top7. These new insights may have important implications on the de novo design of proteins.Optical tweezers experiments reveal that the folding of the C-terminal fragment of Top7 (cFr) is context-dependent. Depending on its neighboring sequence, cFr shows very different folding pathways and folding kinetics. 相似文献
998.
Jun Liu Kelton A. Schleyer Tyrel L. Bryan Changjian Xie Gustavo Seabra Yongmei Xu Arjun Kafle Chao Cui Ying Wang Kunlun Yin Benjamin Fetrow Paul K. P. Henderson Peter Z. Fatland Jian Liu Chenglong Li Hua Guo Lina Cui 《Chemical science》2021,12(1):239
Heparanase (HPA) is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as various types of cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, no structurally defined probes are available for the detection of heparanase activity. Here we present the development of the first ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity via tuning the electronic effect of the substrate. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit. The high sensitivity and robustness of the probe are exemplified in a high-throughput screening assay for heparanase inhibitors.Heparanase, a critical enzyme involved in the remodeling of the extracellular matrix, activates a disaccharide probe HADP to give a strong fluorescence signal. 相似文献
999.
Ab initio molecular orbital theory and density functional theory have been employed to study N14 cluster with low spin at the HF/6-31G*, B3LYP/6-31G*, B3PW91/6-31G*, BP86/6-31G*, and BHLYP/6-31G* levels of theory. Twelve isomers were studied, including one previously investigated cage molecule. The most stable isomer of N14 is a C
2h
-symmetric molecule that contains two separated five-membered nitrogen rings connected by a —N=N—N=N— bridge. The second, third, and fifth most stable isomers each have one five-membered nitrogen ring. The theoretical results suggest that the five-membered nitrogen ring gives rise to a particularly stable structural unit, and the more side chains that the five-membered nitrogen ring links with, the less stable the structure will become. 相似文献
1000.
Yonggyu Han 《Journal of organometallic chemistry》2003,679(1):48-58
Nine thermally stable complexes (η5-Cp*)[η5-(C5H4)CMe2CB10H10CR]MCl2 (R=H and Me) and (η5-Cp*)[η5; η1-(C5H4)CMe2(CB10H10C)]MCl have been prepared via metathesis reactions of Cp*MCl3 (M=Ti, Zr and Hf, Cp*=pentamethylcyclopentadienyl) with monolithium salts of (C5H5)CMe2(CB10H10CR) (R=H and Me) and with dilithium salt of (C5H5)CMe2(CB10H10CH), respectively. These compounds have been fully characterized by various spectroscopic methods and elemental analyses. All of the compounds except (η5-Cp*)[η5-(C5H4)CMe2CB10H10CMe]HfCl2 were additionally characterized by a single crystal X-ray diffraction study, establishing their monomeric bent metallocene structural feature with carborane acting as a substituent or an ancillary ligand. The titanium and zirconium complexes produce high-density polyethylenes with the activity range of about 103-104 g PE per mol of M bar h in the presence of modified methylaluminoxane cocatalyst. 相似文献