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   2664篇
  免费   133篇
  国内免费   15篇
化学   1639篇
晶体学   16篇
力学   133篇
数学   553篇
物理学   471篇
  2023年   24篇
  2022年   50篇
  2021年   78篇
  2020年   74篇
  2019年   55篇
  2018年   48篇
  2017年   49篇
  2016年   120篇
  2015年   113篇
  2014年   110篇
  2013年   173篇
  2012年   203篇
  2011年   199篇
  2010年   98篇
  2009年   111篇
  2008年   176篇
  2007年   144篇
  2006年   126篇
  2005年   110篇
  2004年   104篇
  2003年   92篇
  2002年   69篇
  2001年   34篇
  2000年   32篇
  1999年   22篇
  1998年   20篇
  1997年   26篇
  1996年   18篇
  1995年   13篇
  1994年   20篇
  1993年   18篇
  1992年   18篇
  1991年   18篇
  1990年   15篇
  1989年   21篇
  1988年   16篇
  1987年   9篇
  1986年   10篇
  1985年   17篇
  1984年   21篇
  1983年   11篇
  1982年   14篇
  1981年   19篇
  1980年   11篇
  1979年   13篇
  1978年   5篇
  1977年   7篇
  1976年   5篇
  1974年   6篇
  1969年   4篇
排序方式: 共有2812条查询结果,搜索用时 15 毫秒
131.
Reproducibility among different types of excitation modes is a major bottleneck in the field of tandem mass spectrometry library development in metabolomics. In this study, we specifically evaluated the influence of collision voltage and activation time parameters on tandem mass spectrometry spectra for various excitation modes [collision‐induced dissociation (CID), pulsed Q dissociation (PQD) and higher‐energy collision dissociation (HCD)] of Orbitrap‐based instruments. For this purpose, internal energy deposition was probed using an approach based on Rice–Rampserger–Kassel–Marcus modeling with three thermometer compounds of different degree of freedom (69, 228 and 420) and a thermal model. This model treats consecutively the activation and decomposition steps, and the survival precursor ion populations are characterized by truncated Maxwell–Boltzmann internal energy distributions. This study demonstrates that the activation time has a significant impact on MS/MS spectra using the CID and PQD modes. The proposed model seems suitable to describe the multiple collision regime in the PQD and HCD modes. Linear relationships between mean internal energy and collision voltage are shown for the latter modes and the three thermometer molecules. These results suggest that a calibration based on the collision voltage should provide reproducible for PQD, HCD to be compared with CID in tandem in space instruments. However, an important signal loss is observed in PQD excitation mode whatever the mass of the studied compounds, which may affect not only parent ions but also fragment ions depending on the fragmentation parameters. A calibration approach for the CID mode based on the variation of activation time parameter is more appropriate than one based on collision voltage. In fact, the activation time parameter in CID induces a modification of the collisional regime and thus helps control the orientation of the fragmentation pathways (competitive or consecutive dissociations). Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   
132.
Following a heart attack, more than a billion cardiac muscle cells (cardiomyocytes) can be killed, leading to heart failure and sudden death. Much research in this area is now focused on the regeneration of heart tissue through differentiation of stem cells, proliferation of existing cardiomyocytes and cardiac progenitor cells, and reprogramming of fibroblasts into cardiomyocytes. Different chemical modalities (i.e. methods or agents), ranging from small molecules and RNA approaches (including both microRNA and anti‐microRNA) to modified peptides and proteins, are showing potential to meet this medical need. In this Review, we outline the recent advances in these areas and describe both the modality and progress, including novel screening strategies to identify hits, and the upcoming challenges and opportunities to develop these hits into pharmaceuticals, at which chemistry plays a key role.  相似文献   
133.
The ubiquitin–proteasome system (UPS) has been successfully targeted by both academia and the pharmaceutical industry for oncological and immunological applications. Typical proteasome inhibitors are based on a peptidic backbone endowed with an electrophilic C‐terminus by which they react with the active proteolytic sites. Although the peptide moiety has attracted much attention in terms of subunit selectivity, the target specificity and biological stability of the compounds are largely determined by the reactive warheads. In this study, we have carried out a systematic investigation of described electrophiles by a combination of in vitro, in vivo, and structural methods in order to disclose the implications of altered functionality and chemical reactivity. Thereby, we were able to introduce and characterize the class of α‐ketoamides as the most potent reversible inhibitors with possible applications for the therapy of solid tumors as well as autoimmune disorders.  相似文献   
134.
The MgBr2‐catalyzed formal [3+2] cycloaddition of donor–acceptor activated cyclopropanes with nitrosoarenes offers a novel approach to various structurally diverse isoxazolidines. The reactions, which are experimentally easy to conduct, occur with complete stereospecificity and perfect control of regioselectivity. Product isoxazolidines can be readily transformed into α‐amino lactones by reductive or decarboxylative N? O cleavage and subsequent lactonisation, and the N‐aryl bond cleavage is also possible under oxidative conditions.  相似文献   
135.
The ability to engineer and re‐program the surfaces of cells would provide an enabling synthetic biological method for the design of cell‐ and tissue‐based therapies. A new cell surface‐engineering strategy is described that uses lipid‐chemically self‐assembled nanorings (lipid‐CSANs) that can be used for the stable and reversible modification of any cell surface with a molecular reporter or targeting ligand. In the presence of a non‐toxic FDA‐approved drug, the nanorings were quickly disassembled and the cell–cell interactions reversed. Similar to T‐cells genetically engineered to express chimeric antigen receptors (CARS), when activated peripheral blood mononuclear cells (PBMCs) were functionalized with the anti‐EpCAM‐lipid‐CSANs, they were shown to selectively kill antigen‐positive cancer cells. Taken together, these results demonstrate that lipid‐CSANs have the potential to be a rapid, stable, and general method for the reversible engineering of cell surfaces and cell–cell interactions.  相似文献   
136.
Substitution of chloride in [PtCl(bpma)]+ and [PtCl(gly-met-S,N,N)], where bpma is bis(2-pyridylmethyl)amine and gly-met-S,N,N is glycyl-l-methionine, was studied as a function of the entering nucleophile concentration and temperature. Reactions between the platinum(II) complexes and thiourea (TU), iodides (I?), and nitrites(III) (NO 2 ? ) were carried out in aqueous solutions using conventional UV-VIS spectrophotometry. Suitable ionic conditions were reached by an addition of 0.1 M NaClO4 and 0.01 M NaCl (to suppress hydrolysis). The second-order rate constants, k 2, for the studied reactions with NO 2 ? varied between 0.036–0.038 M?1 s?1, and for the reactions with TU between 0.095–1.06 M?1 s?1, respectively. The reaction between TU and the [PtCl(bpma)]+ ion is ten times faster than that of the [PtCl(gly-met-S,N,N)] complex. An analysis of the activation parameters, ΔH and ΔS , for the selected reactions clearly shows their associative nature.  相似文献   
137.
The inclusion of local anesthetic drug procaine hydrochloride by β-cyclodextrin was investigated by 1D and 2D proton NMR spectroscopy and isothermal titration calorimetry (ITC) at 298 K. The stoichiometry of the complex was determinate by the method of continuous variation, using the chemical induced shift of both host and guest protons. The association constant K, of the obtained complex was calculated and found to be 293.17 M?1. Rotating frame NOE spectroscopy, was used to ascertain the solution geometry of the host–guest complex. The result reveals that the procaine molecule penetrates into the β-cyclodextrin cavity with the aromatic ring. The energetics of complexation process is investigated by ITC technique. The analysis indicates that the complexation of procaine by β-CD is an exothermic process and show that both enthalpy and entropy contribute to the binding process. The obtained value for the association constant is in good agreement with that obtained from NMR.  相似文献   
138.
Hydride abstraction from the heterocyclic carbene borane adducts (NHC)BH2C6F5 (NHC: IMes or IMe4) gave the B−H containing [(NHC)B(H)C6F5]+ borenium cations. They added carbon monoxide to give the respective [(NHC)B(H)(C6F5)CO]+ boron carbonyl cations. Carbon nucleophiles add to the boron carbonyl to give [B](H) acyls. Hydride reduced the [B]CO cation to hydroxymethylborane derivatives.  相似文献   
139.
140.
La3B6O13(OH) was obtained by a high-pressure/high-temperature experiment at 6 GPa and 1673 K. The compound crystallizes in the space group P21 (no. 4) with the lattice parameters a=4.785(2), b=12.880(4), c=7.433(3) Å, and β=90.36(10)°, and is built up of corner- as well as edge-sharing BO4 tetrahedra. It represents the first acentric high-pressure borate containing these B2O6 entities. The compound develops borate layers of „sechser“-rings with the La3+ cations positioned between the layers. Single-crystal and powder X-ray diffraction, vibrational and MAS NMR spectroscopy, second-harmonic generation (SHG) and thermoanalytical measurements, as well as computational methods were used to affirm the proposed structure and the B2O6 entities.  相似文献   
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