全文获取类型
收费全文 | 6432篇 |
免费 | 603篇 |
国内免费 | 588篇 |
专业分类
化学 | 4741篇 |
晶体学 | 22篇 |
力学 | 235篇 |
综合类 | 45篇 |
数学 | 70篇 |
物理学 | 2510篇 |
出版年
2024年 | 13篇 |
2023年 | 101篇 |
2022年 | 203篇 |
2021年 | 220篇 |
2020年 | 268篇 |
2019年 | 245篇 |
2018年 | 180篇 |
2017年 | 329篇 |
2016年 | 353篇 |
2015年 | 301篇 |
2014年 | 400篇 |
2013年 | 404篇 |
2012年 | 474篇 |
2011年 | 415篇 |
2010年 | 311篇 |
2009年 | 354篇 |
2008年 | 382篇 |
2007年 | 398篇 |
2006年 | 326篇 |
2005年 | 295篇 |
2004年 | 317篇 |
2003年 | 209篇 |
2002年 | 180篇 |
2001年 | 120篇 |
2000年 | 120篇 |
1999年 | 125篇 |
1998年 | 114篇 |
1997年 | 111篇 |
1996年 | 71篇 |
1995年 | 60篇 |
1994年 | 42篇 |
1993年 | 43篇 |
1992年 | 24篇 |
1991年 | 28篇 |
1990年 | 25篇 |
1989年 | 16篇 |
1988年 | 9篇 |
1987年 | 14篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 4篇 |
排序方式: 共有7623条查询结果,搜索用时 31 毫秒
991.
Thilini D. Kondasinghe Hasina Y. Saraha Shane T. Jackowski Jennifer L. Stockdill 《Tetrahedron letters》2019,60(1):23-28
α4/7-Conotoxin LvIA is an isoform-selective inhibitor of the α3β2 nicotinic acetylcholine receptor. An efficient strategy for the synthesis of this toxin is critical to advancing its utility as a probe for receptor function and as a potential pharmaceutical lead target. On-resin methods for peptide synthesis offer potential synthetic advantages; however, strategies for on-resin formation of multiple disulfides have historically been low-yielding. Here, we harness the reactivity of the Allocam protecting group and employ a 3-amino acid spacer strategy to synthesize α4/7-conotoxin LvIA via three different on-resin strategies, each of which results in an isolated yield higher than previous fully on-resin approaches. 相似文献
992.
A EuIII-containing single molecule BCR-Eu as design platform for ratio-metric fluorescent sensor which includes a blue-emitting coumarin dye, a green-emitting BODIPY fluorophore and a EuIII moiety as the origin of red light has been designed and synthesized. The compound BCR shows only green emission with large stoke shift when excited in 400 nm due to good fluorescence resonance energy transfer from coumarin to BODIPY. After embedding EuIII complexes in the molecule, BCR-Eu exhibits dual emission which is equal in magnitude and independent of each other, when excited at the range of 305–365 nm. An emission from Lanthanide complexes as the stable built-in standard fluorescence peak offers a promising opportunity to enhance the precision of bioimaging and also an ideal design platform for future ratio-metric fluorescent sensor. 相似文献
993.
The antibiotic pipeline has failed to keep pace with the rise of multidrug resistant tuberculosis and extensively drug-resistant tuberculosis pathogens. Naturally occurring peptides provide a rich source of lead compounds for developing novel pharmaceuticals with high selectivity and potency. Given the vast number of naturally-occurring bioactive cyclic peptides identified so far, the following digest highlights several cyclic peptides, discovered in the preceding decade, that exhibit promising activity against Mycobacterium tuberculosis. 相似文献
994.
Tomohiro Umeno Atsushi Ueda Mitsunobu Doi Takuma Kato Makoto Oba Masakazu Tanaka 《Tetrahedron letters》2019,60(49):151301
The introduction of a five-membered ring α,α-disubstituted α-amino acid into l-Leu-based heptapeptides preferentially induced right-handed (P) helical structures. Using 5 ~ 20 mol% of a single helical foldamers-catalyst, enantioselective 1,4-addition reactions of dialkyl malonates to cycloalk-2-enones (5 ~ 7 rings) proceeded to give chiral 3-substituted cycloalkanones with 94 ~ 99% ee in moderate chemical yields, regardless of the ring size of substrates. 相似文献
995.
Yizhen Yin Qianran Fei Weidong Liu Zhuoru Li Hiroaki Suga Chuanliu Wu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(15):4934-4939
Bicyclic and tricyclic peptides have emerged as promising candidates for the development of protein binders and new therapeutics. However, convenient and efficient strategies that can generate topologically controlled bicyclic and tricyclic peptide scaffolds from fully‐unprotected peptides are still much in demand, particularly for those amenable to the design of biosynthetic libraries. In this work, we report a reliable chemical and ribosomal synthesis of topologically controlled bicyclic and tricyclic peptide scaffolds. Our strategy involves the combination of selenoether cyclization followed by disulfide or thioether cyclization, yielding desirable bicyclic and tricyclic peptides. This work thus lays the foundation for developing peptide libraries with controlled topology of multicyclic scaffolds for in vitro display techniques. 相似文献
996.
Huawu Yin David J. Craik Conan K. Wang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(23):7734-7738
Loops at protein–protein interfaces are a rich source of peptide leads that have high specificity and low toxicity. Although such peptides typically need to be constrained to overcome thermodynamic and metabolic limitations, design guidelines to obtain a successfully constrained peptides, and thus facilitate the transition from loop to drug, are relatively poorly formulated. In this work, we surveyed the structures of interface loops and found the position of the terminal residues to be a key determinant of conformation. We used this knowledge to improve the process of molecular grafting, a valuable approach for constraining and stabilising peptides by fusing them to a suitable scaffold. We show that an informed choice of where a loop is “anchored” to a scaffold improves its form and function. This knowledge can help guide the choice of loop and its matching scaffold, and thus increase the success rate for designing stable and potent peptide drug leads. 相似文献
997.
Peng Teng Geoffrey M. Gray Mengmeng Zheng Sylvia Singh Xiaopeng Li Lukasz Wojtas Arjan vanderVaart Jianfeng Cai 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(23):7860-7864
Peptide‐mediated self‐assembly is a prevalent method for creating highly ordered supramolecular architectures. Herein, we report the first example of orthogonal C?X???X?C/C?X???π halogen bonding and hydrogen bonding driven crystalline architectures based on synthetic helical peptides bearing hybrids of l ‐sulfono‐γ‐AApeptides and natural amino acids. The combination of halogen bonding, intra‐/intermolecular hydrogen bonding, and intermolecular hydrophobic interactions enabled novel 3D supramolecular assembly. The orthogonal halogen bonding in the supramolecular architecture exerts a novel mechanism for the self‐assembly of synthetic peptide foldamers and gives new insights into molecular recognition, supramolecular design, and rational design of biomimetic structures. 相似文献
998.
Libing Zhang Zongjie Wang Jagotamoy Das Mahmoud Labib Sharif Ahmed Edward H. Sargent Shana O. Kelley 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(41):14661-14665
In living systems, interfacial molecular interactions control many biological processes. New stimuli‐responsive strategies are desired to provide versatile model systems that can regulate cell behavior in vitro. Described here are potential‐responsive surfaces that control cell adhesion and release as well as stem cell differentiation. Cell adhesion can be modulated dynamically by applying negative and positive potentials to surfaces functionalized with tailored monolayers. This process alters cell morphology and ultimately controls behavior and the fate of the cells. Cells can be detached from the electrode surface as intact clusters with different geometries using electrochemical potentials. Importantly, morphological changes during adhesion guide stem cell differentiation. The higher accessibility of the peptide under a positive applied potential causes phenotypic changes in the cells that are hallmarks of osteogenesis, whereas lower accessibility of the peptide promoted by negative potentials leads to adipogenesis. 相似文献
999.
Tianlu Mo Xinjian Ji Wei Yuan Dhanaraju Mandalapu Fangting Wang Yuting Zhong Fuyou Li Qin Chen Wei Ding Zixin Deng Shaoning Yu Qi Zhang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(52):18969-18973
Sactionine‐containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post‐translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S‐adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow‐spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin‐sectioning transmission electron microscopy, scanning electron microscopy, and large‐unilamellar‐vesicle‐based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization. 相似文献
1000.
Xiaoshan Shayna Wang Peng‐Hsun Chase Chen J. Trae Hampton Jeffery M. Tharp Catrina A. Reed Sukant K. Das Duen‐Shian Wang Hamed S. Hayatshahi Yang Shen Jin Liu Wenshe Ray Liu 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(44):16051-16056
Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic‐peptide ligands for therapeutic targets, phage‐displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage‐display technique in which its displayed peptides are cyclized through a proximity‐driven Michael addition reaction between a cysteine and an amber‐codon‐encoded N?‐acryloyl‐lysine (AcrK). Using a randomized 6‐mer library in which peptides were cyclized at two ends through a cysteine–AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4‐ to 6‐fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery. 相似文献