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51.
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
52.
In Situ Synthesis of Alkenyl Tetrazines for Highly Fluorogenic Bioorthogonal Live‐Cell Imaging Probes 下载免费PDF全文
Dr. Haoxing Wu Dr. Jun Yang Dr. Jolita Šečkutė Prof. Neal K. Devaraj 《Angewandte Chemie (International ed. in English)》2014,53(23):5805-5809
In spite of the wide application potential of 1,2,4,5‐tetrazines, particularly in live‐cell and in vivo imaging, a major limitation has been the lack of practical synthetic methods. Here we report the in situ synthesis of (E)‐3‐substituted 6‐alkenyl‐1,2,4,5‐tetrazine derivatives through an elimination–Heck cascade reaction. By using this strategy, we provide 24 examples of π‐conjugated tetrazine derivatives that can be conveniently prepared from tetrazine building blocks and related halides. These include tetrazine analogs of biological small molecules, highly conjugated buta‐1,3‐diene‐substituted tetrazines, and a diverse array of fluorescent probes suitable for live‐cell imaging. These highly conjugated probes show very strong fluorescence turn‐on (up to 400‐fold) when reacted with dienophiles such as cyclopropenes and trans‐cyclooctenes, and we demonstrate their application for live‐cell imaging. This work provides an efficient and practical synthetic methodology for tetrazine derivatives and will facilitate the application of conjugated tetrazines, particularly as fluorogenic probes for live‐cell imaging. 相似文献
53.
PEG接枝氧化石墨烯的制备与细胞成像 总被引:1,自引:0,他引:1
通过酯化反应将不同分子量的聚乙二醇(PEG)接枝到氧化石墨烯(GO)表面,得到系列GO-PEG。利用傅里叶变换红外光谱(FTIR)、拉曼光谱(Raman)、扫描电子显微镜(SEM)对GO-PEG的结构和形貌进行了表征,用热重分析(TGA)测定了GO-PEG中PEG的接枝量。SEM结果表明GO-PEG的剥离程度高于GO。GO-PEG在磷酸盐缓冲溶液中具有良好的分散稳定性,稳定性与接枝量呈正相关。GO-PEG通过非共价键合作用对荧光素(Flu)的负载量可达1.75 mg·mg-1,且负载量受接枝量影响;另外,GO-PEG对Flu的释放行为具有pH值触发药物释放性能。将接枝PEG的端羟基与Flu共价键合,所得GO-PEG6000-Flu荧光探针实现了对HepG2细胞的成像。 相似文献
54.
Stepan Geri Tereza Krunclova Dr. Olga Janouskova Dr. Jiri Panek Dr. Martin Hruby Daniel Hernández-Valdés Dr. Benjamin Probst Prof. Roger A. Alberto Dr. Constantin Mamat Dr. Manja Kubeil Dr. Holger Stephan 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(48):10992-11006
Two photoactivatable dicarbonyl ruthenium(II) complexes based on an amide-functionalised bipyridine scaffold (4-position) equipped with an alkyne functionality or a green-fluorescent BODIPY (boron-dipyrromethene) dye have been prepared and used to investigate their light-induced decarbonylation. UV/Vis, FTIR and 13C NMR spectroscopies as well as gas chromatography and multivariate curve resolution alternating least-squares analysis (MCR-ALS) were used to elucidate the mechanism of the decarbonylation process. Release of the first CO molecule occurs very quickly, while release of the second CO molecule proceeds more slowly. In vitro studies using two cell lines A431 (human squamous carcinoma) and HEK293 (human embryonic kidney cells) have been carried out in order to characterise the anti-proliferative and anti-apoptotic activities. The BODIPY-labelled compound allows for monitoring the cellular uptake, showing fast internalisation kinetics and accumulation at the endoplasmic reticulum and mitochondria. 相似文献
55.
56.
Cellular Automaton (CA) based traffic flow models have been extensively studied due to their effectiveness and simplicity in recent years. This paper develops a discrete time Markov chain (DTMC) analytical framework for a Nagel-Schreckenberg and Fukui Ishibashi combined CA model (W^2H traffic flow model) from microscopic point of view to capture the macroscopic steady state speed distributions. The inter-vehicle spacing Maxkov chain and the steady state speed Markov chain are proved to be irreducible and ergodic. The theoretical speed probability distributions depending on the traffic density and stochastic delay probability are in good accordance with numerical simulations. The derived fundamental diagram of the average speed from theoretical speed distributions is equivalent to the results in the previous work. 相似文献
57.
The class of quantum languages Q() over an alphabet is the class of languages accepted by quantum automata. We study properties of Q() and compare Q() with the class of regular languages R(). It is shown that Q() is closed under union, intersection, and reversal but is not closed under complementation, concatenation, or Kleene star. It is also shown that Q() and R() are incomparable. Finally, we prove that L Q() if and only if L admits a transition amplitude function satisfying a certain property and a similar characterization is given for R(). 相似文献
58.
Tom Bohman 《Transactions of the American Mathematical Society》1999,351(3):947-983
In the discrete threshold model for crystal growth in the plane we begin with some set of seed crystals and observe crystal growth over time by generating a sequence of subsets of by a deterministic rule. This rule is as follows: a site crystallizes when a threshold number of crystallized points appear in the site's prescribed neighborhood. The growth dynamics generated by this model are said to be omnivorous if finite and imply . In this paper we prove that the dynamics are omnivorous when the neighborhood is a box (i.e. when, for some fixed , the neighborhood of is . This result has important implications in the study of the first passage time when is chosen randomly with a sparse Bernoulli density and in the study of the limiting shape to which converges.
59.
Parrondo games are coin flipping games with the surprising property that alternating plays of two losing games can produce a winning game. We show that this phenomenon can be modelled by probabilistic lattice gas automata. Furthermore, motivated by the recent introduction of quantum coin flipping games, we show that quantum lattice gas automata provide an interesting definition for quantum Parrondo games. 相似文献
60.
We study numerically the nature of the diffusion process on a honeycomb and a quasi-lattice, where a point particle, moving along the bonds of the lattice, scatters from randomly placed scatterers on the lattice sites according to strictly deterministic rules. For the honeycomb lattice fully occupied by fixed rotators two (symmetric) isolated critical points appear to be present, with the same hyperscaling relation as for the square and the triangular lattices. No such points appear to exist for the quasi-lattice. A comprehensive comparison is made with the behavior on the previously studied square and triangular lattices. A great variety of diffusive behavior is found, ranging from propagation, superdiffusion, normal, quasi-normal, and anomalous, to absence of diffusion. The influence of the scattering rules as well as of the lattice structure on the diffusive behavior of a point particle moving on the all lattices studied so far is summarized. 相似文献