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Laura M. Luh Ulrike Scheib Katrin Juenemann Lars Wortmann Michael Brands Philipp M. Cromm 《Angewandte Chemie (International ed. in English)》2020,59(36):15448-15466
Targeted protein degradation (TPD), the ability to control a proteins fate by triggering its degradation in a highly selective and effective manner, has created tremendous excitement in chemical biology and drug discovery within the past decades. The TPD field is spearheaded by small molecule induced protein degradation with molecular glues and proteolysis targeting chimeras (PROTACs) paving the way to expand the druggable space and to create a new paradigm in drug discovery. However, besides the therapeutic angle of TPD a plethora of novel techniques to modulate and control protein levels have been developed. This enables chemical biologists to better understand protein function and to discover and verify new therapeutic targets. This Review gives a comprehensive overview of chemical biology techniques inducing TPD. It explains the strengths and weaknesses of these methods in the context of drug discovery and discusses their future potential from a medicinal chemist's perspective. 相似文献
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Mössbauer spectra of KSnBr3·2H2O were very broad and could not fit Lorentz equation, suggesting unresolvable quadrupole doublets. Its quadrupole splitting was estimated to be about 0.25 mm/s from the separate experiments on frozen aqueous solutions of Sn(II)-Br? systems. Stability constants of bromostannate(II) complexes were determined at μ = 3.5 from the Δ-cL curve by the approximation method, which were in agreement with the literature values. 相似文献
45.
An optical-optical double resonance sub-Doppler experiment is used to measure short nonradiative lifetimes in the C (1)Sigma(+) state of LiH. These lifetimes are expected to result from the strong electronic interaction between the C (1)Sigma(+) state and the continuum of the A (1)Sigma(+) state and to vary with the vibrational quantum number, from nanoseconds to milliseconds. The experimental setup combines a molecular beam of LiH, a first cw laser beam locked to a given A-X absorption line, and a second cw laser beam scanned over C-A absorption profiles. Analysis of these absorption profiles in terms of Voigt profiles shows that their Lorentzian components significantly vary with the vibrational quantum numbers of the C state. Nonradiative decay rates deduced this way are systematically larger than the calculated ones but their variations are similar. Coherent saturation effects cannot be invoked to explain this discrepancy. 相似文献
46.
The phosphine-containing polymer 1 is obtained by ruthenium-catalyzed ring-opening metathesis polymerization of the norbornene derivative 2. Polymer 1 is employed as the polymer support in the palladium-catalyzed Heck, Sonogashira, and Negishi reactions, and the corresponding (methoxymethylphenyl)diphenylphosphine (6) ligand is used for comparison. The polymer-supported catalysts retain most of their catalytic activities in these coupling reactions in the recycling processes. 相似文献
47.
Excimer Formation in a Confined Space: Photophysics of Ladderphanes with Tetraarylethylene Linkers
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Dr. Chih‐Hsien Chen Kamani Satyanarayana Yi‐Hung Liu Shou‐Ling Huang Prof. Tsong‐Shin Lim Prof. Tien‐Yau Luh 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(2):800-807
Communication between chromophores is vital for both natural and non‐natural photophysical processes. Spatial confinements offer unique conditions to scrutinize such interactions. Polynorbornene‐ and polycyclobutene‐based ladderphanes are ideal model compounds in which all tetraarylethylene (TAE) linkers are aligned coherently. The spans for each of the monomeric units in these ladderphanes are 4.5–5.5 Å. Monomers do not exhibit emission, because bond rotation in TAE can quench the excited‐state energy. However, polymers emit at 493 nm (Φ=0.015) with large Stokes shift under ambient conditions and exhibit dual emission at 450 and 493 nm at 150 K. When the temperature is lowered, the emission intensity at 450 nm increases, whereas that at 493 nm decreases. At 100 K, both monomers and polymers emit only at 450 nm. This shorter‐wavelength emission arises from the intrinsic emission of TAE chromophore, and the emission at 493 nm could be attributed to the excimer emission in the confined space of ladderphanes. The fast kinetics suggest diffusion‐controlled formation of the excimer. 相似文献
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I Made Agus Gelgel Wirasuta Ni Made Amelia Ratnata Dewi Kadek Duwi Cahyadi Luh Putu Mirah Kusuma Dewi Ni Made Widi Astuti I Nyoman Kadjeng Widjaja 《Chromatographia》2013,76(19-20):1261-1269
The decision limit (CCα), capability of detection (CCβ) and quantification limit (QL) are importance performance characteristics in method validation. The TLC-Scanner 3 from Camag provides the possibility to choose the slit dimension of light to determine the peak chromatogram of a substance. The influence of the slit dimension for determination of CCα, CCβ and QL of paracetamol has been carried out. Paracetamol was spotted onto plates of AL-TLC Si G 60 F254 by linomat 4 in the range of 50–400 ng/spot and 10–400 ng/band, then on twin chambers eluted with TAEA (toluene:acetone-ethanol:conc.ammonia, 45 + 45 + 7 + 3 v/v) for 45 mm. Eluted spots were scanned in different slit dimensions at 248 nm. The CCα, CCβ and QL of paracetamol were estimated through the linear regression (LRM) and signal-to-noise (S/N) methods. Slit lengths between 50 and 133 % of the band width of the spots, and with the noise factor of the slit under 2.6, produced good precision measurements of TLC-densitometry between plates, while slit lengths between 50 and 83 % of the band width of the spots introduced a higher sensitivity response of the detector. The estimated CCα, CCβ and QL were determined by how the data were collected, the analytical optical setting, and the usage method for the estimation of both validation parameters. 相似文献
49.
In this paper, an M/G/1 queue with exponentially working vacations is analyzed. This queueing system is modeled as a two-dimensional embedded Markov chain which has an M/G/1-type transition probability matrix. Using the matrix analytic method, we obtain the distribution for the stationary queue length at departure epochs. Then, based on the classical vacation decomposition in the M/G/1 queue, we derive a conditional stochastic decomposition result. The joint distribution for the stationary queue length and service status at the arbitrary epoch is also obtained by analyzing the semi-Markov process. Furthermore, we provide the stationary waiting time and busy period analysis. Finally, several special cases and numerical examples are presented. 相似文献
50.
[reaction: see text] Olefination of aliphatic dithioacetals with Grignard reagents is catalyzed by Ni(acac)(2) in the presence of an appropriate trialkylphosphine ligand. 相似文献