全文获取类型
收费全文 | 3715篇 |
免费 | 109篇 |
国内免费 | 30篇 |
专业分类
化学 | 2221篇 |
晶体学 | 32篇 |
力学 | 131篇 |
数学 | 640篇 |
物理学 | 830篇 |
出版年
2023年 | 26篇 |
2022年 | 55篇 |
2021年 | 66篇 |
2020年 | 75篇 |
2019年 | 73篇 |
2018年 | 71篇 |
2017年 | 53篇 |
2016年 | 112篇 |
2015年 | 110篇 |
2014年 | 124篇 |
2013年 | 214篇 |
2012年 | 243篇 |
2011年 | 309篇 |
2010年 | 176篇 |
2009年 | 163篇 |
2008年 | 228篇 |
2007年 | 197篇 |
2006年 | 210篇 |
2005年 | 184篇 |
2004年 | 152篇 |
2003年 | 128篇 |
2002年 | 88篇 |
2001年 | 72篇 |
2000年 | 56篇 |
1999年 | 33篇 |
1998年 | 41篇 |
1997年 | 39篇 |
1996年 | 40篇 |
1995年 | 27篇 |
1994年 | 25篇 |
1993年 | 29篇 |
1992年 | 21篇 |
1991年 | 11篇 |
1990年 | 17篇 |
1988年 | 11篇 |
1987年 | 9篇 |
1986年 | 14篇 |
1985年 | 34篇 |
1984年 | 35篇 |
1983年 | 19篇 |
1982年 | 21篇 |
1981年 | 16篇 |
1980年 | 19篇 |
1979年 | 18篇 |
1978年 | 19篇 |
1977年 | 18篇 |
1976年 | 19篇 |
1974年 | 9篇 |
1973年 | 15篇 |
1972年 | 9篇 |
排序方式: 共有3854条查询结果,搜索用时 15 毫秒
101.
Maria-Agustina Rossi Veronica Martinez Philip Hinchliffe Maria F. Mojica Valerie Castillo Diego M. Moreno Ryan Smith Brad Spellberg George L. Drusano Claudia Banchio Robert A. Bonomo James Spencer Alejandro J. Vila Graciela Mahler 《Chemical science》2021,12(8):2898
Infections caused by multidrug resistant (MDR) bacteria are a major public health threat. Carbapenems are among the most potent antimicrobial agents that are commercially available to treat MDR bacteria. Bacterial production of carbapenem-hydrolysing metallo-β-lactamases (MBLs) challenges their safety and efficacy, with subclass B1 MBLs hydrolysing almost all β-lactam antibiotics. MBL inhibitors would fulfil an urgent clinical need by prolonging the lifetime of these life-saving drugs. Here we report the synthesis and activity of a series of 2-mercaptomethyl-thiazolidines (MMTZs), designed to replicate MBL interactions with reaction intermediates or hydrolysis products. MMTZs are potent competitive inhibitors of B1 MBLs in vitro (e.g., Ki = 0.44 μM vs. NDM-1). Crystal structures of MMTZ complexes reveal similar binding patterns to the most clinically important B1 MBLs (NDM-1, VIM-2 and IMP-1), contrasting with previously studied thiol-based MBL inhibitors, such as bisthiazolidines (BTZs) or captopril stereoisomers, which exhibit lower, more variable potencies and multiple binding modes. MMTZ binding involves thiol coordination to the Zn(ii) site and extensive hydrophobic interactions, burying the inhibitor more deeply within the active site than d/l-captopril. Unexpectedly, MMTZ binding features a thioether–π interaction with a conserved active-site aromatic residue, consistent with their equipotent inhibition and similar binding to multiple MBLs. MMTZs penetrate multiple Enterobacterales, inhibit NDM-1 in situ, and restore carbapenem potency against clinical isolates expressing B1 MBLs. Based on their inhibitory profile and lack of eukaryotic cell toxicity, MMTZs represent a promising scaffold for MBL inhibitor development. These results also suggest sulphur–π interactions can be exploited for general ligand design in medicinal chemistry.Metallo-β-lactamases (MBLs) are major culprits of resistance to carbapenems in bacteria. A series of thiazolidines are potent MBL inhibitors, restoring the activity of carbapenems. Metal binding and sulphur–π interactions are key to inhibition. 相似文献
102.
The reactions of 1-bromo-, 1-iodo-, 2-bromo-, 1,3-dibromo-, and 1,4-dibromoadamantane with Me(3)Sn(-) ions were studied in liquid ammonia. The photostimulated reaction of 1-haloadamantane (1-XAd, X = Br, I) or 2-BrAd with Me(3)Sn(-) ions gave in a few minutes excellent yields of the substitution products. The 1,3-dibromo- and 1,4-dibromoadamantane with Me(3)Sn(-) ions also reacted very fast under irradiation to give the disubstitution product in good yields. In competition experiments, 1-ClAd is 5.3 times more reactive than 5-chloro-2-adamantanone (9) toward Me(3)Sn(-) ions in liquid ammonia. When the nucleophile is the Ph(2)P(-) ion, 1-ClAd reacts 2.4 times faster than 9. This is the first time that no redox catalysis was observed when the bridgehead compound bears a carbonyl group as a pi acceptor. On the other hand, the nucleophile Me(3)Sn(-) ion was ca. >1000 times more reactive than Ph(3)Sn(-) ions toward 1-adamantyl radicals, in contrast to the behavior of aryl radicals, where both nucleophiles have the same reactivity. 相似文献
103.
Oliveira SC Paiva TC Visconti AE Giudici R 《Applied biochemistry and biotechnology》1998,74(3):161-172
Discrimination between different rival models for describing the inhibitory effect of ethanol both on yeast growth and on
fermentation was studied for a continuous process of alcoholic fermentation in a tower reactor with recycling of flocculating
cells. Models tested include linear, parabolic, hyperbolic, exponential, and generalized nonlinear power-law types. The best
expressions were identified under the criteria that all the kinetic parameters should assume acceptable values in a feasible
range and should result in the best fit of the experimental data. The kinetic parameters were estimated from steady-state
data of several sugar concentrations in feeding stream (S0 = 160, 170, 180, 190, 200 g/L), constant dilution rate (D = 0.2 h-1), recycle ratio (α = 13.6), and temperature (T = 30°C). The best model for the yeast growth was of power-law type, whereas
for the product formation the best model was of linear type. These models were able to reproduce the trends of the process
variables satisfactorily. 相似文献
104.
105.
T. A. Armstrong M. Benayoun I. J. Bloodworth J. N. Carney C. J. Dodenhoff C. Evangelista B. R. French B. Ghidini M. Girone A. Jacholkowski J. Kahane J. B. Kinson A. Kirk K. Knudson V. Lenti Ph. Leruste A. Malamant J. L. Narjoux F. Navach A. Palano N. Redaelli L. Rossi M. Sené R. Sené M. Stassinaki G. Vassiliadis O. Villalobos Baillie M. F. Votruba G. Zito 《Zeitschrift fur Physik C Particles and Fields》1992,56(1):29-36
We have studied the reactions \(({{\pi ^ + } \mathord{\left/ {\vphantom {{\pi ^ + } p}} \right. \kern-0em} p})p \to ({{\pi ^ + } \mathord{\left/ {\vphantom {{\pi ^ + } p}} \right. \kern-0em} p})(K\bar K\pi )p\) where the \(K\bar K\pi \) system is centrally produced, at 85 GeV/c and 300 GeV/c using the CERN Omega spectrometer. A spin-parity analysis of theK S 0 K ± π ? system shows the presence of a strongJ PC=1++ signal which we identify as theE/f 1 (1420) meson. We also find evidence for the decayE/f 1(1420)→K S 0 K S 0 π 0 which determines theC-parity of this state to be positive. Alternative explanations of the data have been tested and ruled out. Hence we obtain the quantum numbers of theE/f 1 (1420) to beI G(JPC)=0+(1+). 相似文献
106.
107.
108.
109.
McColl IH Blanch EW Gill AC Rhie AG Ritchie MA Hecht L Nielsen K Barron LD 《Journal of the American Chemical Society》2003,125(33):10019-10026
The vibrational Raman optical activity (ROA) spectrum of a polypeptide in a model beta-sheet conformation, that of poly(l-lysine), was measured for the first time, and the alpha-helix --> beta-sheet transition monitored as a function of temperature in H(2)O and D(2)O. Although no significant population of a disordered backbone state was detected at intermediate temperatures, some side chain bands not present in either the alpha-helix or beta-sheet state were observed. The observation of ROA bands in the extended amide III region assigned to beta-turns suggests that, under our experimental conditions, beta-sheet poly(L-lysine) contains up-and-down antiparallel beta-sheets based on the hairpin motif. The ROA spectrum of beta-sheet poly(L-lysine) was compared with ROA data on a number of native proteins containing different types of beta-sheet. Amide I and amide II ROA band patterns observed in beta-sheet poly(L-lysine) are different from those observed in typical beta-sheet proteins and may be characteristic of an extended flat multistranded beta-sheet, which is unlike the more irregular and twisted beta-sheet found in most proteins. However, a reduced isoform of the truncated ovine prion protein PrP(94-233) that is rich in beta-sheet shows amide I and amide II ROA bands similar to those of beta-sheet poly(L-lysine), which suggests that the C-terminal domain of the prion protein is able to support unusually flat beta-sheets. A principal component analysis (PCA) that identifies protein structural types from ROA band patterns provides a useful representation of the structural relationships among the polypeptide and protein states considered in the study. 相似文献
110.
Starting from 1-tert-butyloxycarbonyl-3-methyl-4-ethoxycarbonyl-1,2-diaza-1,3-diene and β,β,β and α,β-substituted enamines a careful choice of solvents and temperatures allows the divergent synthesis of 5,6-dihydro-4H-pyridazines, 2-(1-N-boc-hydrazono-ethyl)-4-pyrrolidin-1-yl-but-3-enoic acid ethyl ester, and 1-amino-pyrroles. Moreover, some interesting conclusions about the mechanism(s) of the reaction have been drawn by careful analysis of products' structure and distribution. Thus, the reaction may proceed through a stereospecific [4+2] cycloaddition mechanism giving rise to 5,6-dihydro-4H-pyridazines or by simple addition or domino addition/cyclization pathways affording, respectively, 2-(1-N-boc-hydrazono-ethyl)-4-pyrrolidin-1-yl-but-3-enoic acid ethyl ester and 1-amino-pyrroles (formally the [3+2] cycloaddition product). 相似文献