首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   491篇
  免费   14篇
化学   485篇
晶体学   1篇
力学   5篇
数学   4篇
物理学   10篇
  2023年   1篇
  2021年   3篇
  2020年   3篇
  2019年   3篇
  2017年   1篇
  2016年   6篇
  2015年   5篇
  2014年   12篇
  2013年   7篇
  2012年   14篇
  2011年   16篇
  2010年   5篇
  2009年   23篇
  2008年   29篇
  2007年   24篇
  2006年   24篇
  2005年   33篇
  2004年   19篇
  2003年   26篇
  2002年   43篇
  2001年   29篇
  2000年   30篇
  1999年   25篇
  1998年   18篇
  1997年   10篇
  1996年   15篇
  1995年   7篇
  1994年   13篇
  1993年   2篇
  1992年   5篇
  1991年   13篇
  1990年   4篇
  1989年   4篇
  1988年   6篇
  1987年   5篇
  1986年   3篇
  1985年   1篇
  1984年   3篇
  1981年   4篇
  1979年   1篇
  1978年   2篇
  1977年   3篇
  1976年   2篇
  1975年   2篇
  1974年   1篇
排序方式: 共有505条查询结果,搜索用时 15 毫秒
91.
A seven‐step cascade reaction —in which selective mesylation, epoxide formation, epoxide lysis, cyclization, reiterative oxidation, and nitrogen–oxygen exchange occur sequentially—facilitates the construction of the maleic anhydride moiety of CP molecules 1 and 2 (>93% yield per step). Unstable intermediates of this reaction sequence were detected, providing evidence for the proposed mechanism and resulting in the discovery of a new chemical entity.  相似文献   
92.

Background  

Neurotrophins are important regulators of growth and regeneration, and acutely, they can modulate the activity of voltage-gated ion channels. Previously we have shown that acute brain-derived neurotrophic factor (BDNF) activation of neurotrophin receptor tyrosine kinase B (TrkB) suppresses the Shaker voltage-gated potassium channel (Kv1.3) via phosphorylation of multiple tyrosine residues in the N and C terminal aspects of the channel protein. It is not known how adaptor proteins, which lack catalytic activity, but interact with members of the neurotrophic signaling pathway, might scaffold with ion channels or modulate channel activity.  相似文献   
93.
Ever since the world‐shaping discovery of penicillin, nature's molecular diversity has been extensively screened for new medications and lead compounds in drug discovery. The search for agents intended to combat infectious diseases has been of particular interest and has enjoyed a high degree of success. Indeed, the history of antibiotics is marked with impressive discoveries and drug‐development stories, the overwhelming majority of which have their origin in natural products. Chemistry, and in particular chemical synthesis, has played a major role in bringing naturally occurring antibiotics and their derivatives to the clinic, and no doubt these disciplines will continue to be key enabling technologies. In this review article, we highlight a number of recent discoveries and advances in the chemistry, biology, and medicine of naturally occurring antibiotics, with particular emphasis on total synthesis, analogue design, and biological evaluation of molecules with novel mechanisms of action.  相似文献   
94.
The key building blocks (6, 7, and 8) for the intended construction of the originally proposed structures of azaspiracid-1, a potent marine-derived neurotoxin, were coupled and the products elaborated to the targeted compounds (1a,b) and their C-20 epimers (2 and 3). The assembly of the three intermediates was accomplished by a dithiane-based coupling reaction that united the C(1)-C(20) (7) and C(21)-C(27) (8) fragments, followed by a Stille-type coupling which allowed the incorporation of the C(28)-C(40) fragment (6) into the growing substrate. Neither of the final products (1a,b) matched the natural substance by TLC or (1)H NMR spectroscopic analysis, suggesting one or more errors in the originally proposed structure for this notorious biotoxin.  相似文献   
95.
We have studied a donor-acceptor fluorophore-labeled DNA switch where the acceptor is Alexa-647, a carbocyanine dye, in solution at the single molecule level to elucidate the fluorescence switching mechanism. The acceptor, which is in an initial high fluorescence trans state, undergoes a photoisomerization reaction resulting in two additional states during its sub-millisecond transit across the probe volume. These two states are assigned to a nonfluorescent triplet trans state that strongly quenches the donor emission and a singlet cis state that blocks the fluorescence resonance energy transfer (FRET) pathway and gives rise to donor-only fluorescence. The formation of these states is faster than the transit time, so that all three states are approximately equally populated under our experimental conditions. The acceptor dye can stick to the DNA in all these states, with the rate of unsticking determining the rate of isomerization into the other states. Measurement of the rate of change of the FRET signal therefore provides information about the fluorophore-DNA intramolecular dynamics. These results explain the large zero peak in the proximity ratio, often seen in single molecule FRET experiments, and suggest that photoinduced effects may be important in single molecule FRET experiments using carbocyanine dyes. They also suggest that for fast photoinduced switching the interactions of the acceptor dye with the DNA and other surfaces should be prevented.  相似文献   
96.
BACKGROUND: Numerous analogs of the antitumor agents epothilones A and B have been synthesized in search of better pharmacological profiles. Insights into the structure-activity relationships within the epothilone family are still needed and more potent and selective analogs of these compounds are in demand, both as biological tools and as chemotherapeutic agents, especially against drug-resistant tumors. RESULTS: A series of pyridine epothilone B analogs were designed, synthesized and screened. The synthesized compounds exhibited varying degrees of tubulin polymerization and cytotoxicity properties against a number of human cancer cell lines depending on the location of the nitrogen atom and the methyl substituent within the pyridine nucleus. CONCLUSIONS: The biological screening results in this study established the importance of the nitrogen atom at the ortho position as well as the beneficial effect of a methyl substituent at the 4- or 5-position of the pyridine ring. Two pyridine epothilone B analogs (i.e. compounds 3 and 4) possessing higher potencies against drug-resistant tumor cells than epothilone B, the most powerful of the naturally occurring epothilones, were identified.  相似文献   
97.
A direct comparison between photoemission measurements and band structure calculations is sometimes tricky. Matrix element effects may affect considerably the spectral weight of the electronic states and prevent the expected translational symmetry of the band structure from being observed. We show how matrix element effects can be qualitatively described to a certain extent by making an analogy between photoemission and low energy electron diffraction. We have tested this approach in two superperiodic systems. We have first explained the intensity distribution in different Brillouin zones of a surface state in Si(1 1 1)-(7 × 7), where the surface state spectral intensity does not exhibit the (7 × 7) symmetry. We have also compared the LEED intensity of superperiodic LEED spots with the energy dependence of bulk bands on a facetted Si surface as measured by photoemission.  相似文献   
98.
In combining spin- and symmetry-resolved photoemission, magnetotransport measurements and ab initio calculations we detangled the electronic states involved in the electronic transport in Fe(1-x)Co(x)(001)/MgO/Fe(1-x)Co(x)(001) magnetic tunnel junctions. Contrary to previous theoretical predictions, we observe a large reduction in TMR (from 530 to 200% at 20 K) for Co content above 25 atomic% as well as anomalies in the conductance curves. We demonstrate that these unexpected behaviors originate from a minority spin state with Δ(1) symmetry that exists below the Fermi level for high Co concentration. Using angle-resolved photoemission, this state is shown to be a two-dimensional state that occurs at both Fe(1-x)Co(x)(001) free surface, and more importantly at the interface with MgO. The combination of this interface state with the peculiar density of empty states due to chemical disorder allows us to describe in details the complex conduction behavior in this system.  相似文献   
99.
The aim of this work is the development, validation and application of an MEKC method for the chiral separation of Huperzine A. Huperzine A is an important compound that is used to treat Alzheimer's disease. However, only the (?)‐form of this compound is biologically active and behaves as a potential acetylcholinesterase inhibitor. Therefore, the separation of the (?)‐form from the (+)‐form is of greatest importance. Optimal conditions, regarding resolution and analysis time, were established by altering several experimental parameters, such as temperature, field strength, pH, type and concentration of BGE and chiral selector. A major problem that had to be solved in this study was the low intensity and efficiency of the peaks. More parameters were examined, such as the addition of modifiers, to optimize further the separation, and particularly the efficiency. Baseline enantioseparation was achieved by using a BGE of 50 mM acetate (pH 5.0), supplemented with 0.2% w/v poly(sodium N‐undecanoyl‐ll ‐alanyl‐valinate) and 10% v/v tert‐butanol. Finally, the optimum conditions were applied to a pharmaceutical formulation, to demonstrate the ability of the method to control the purity of the (?)‐Huperzine A in pharmaceutical formulations.  相似文献   
100.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号