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821.
Jennifer R. Baker Peter J. Cossar Mark A. T. Blaskovich Alysha G. Elliott Johannes Zuegg Matthew A. Cooper Peter J. Lewis Adam McCluskey 《Molecules (Basel, Switzerland)》2022,27(7)
Five focused compound libraries (forty-nine compounds), based on prior studies in our laboratory were synthesized and screened for antibiotic and anti-fungal activity against S. aureus, E. coli, K. pneumoniae, P. aeruginosa, A. baumannii, C. albicans and C. neoformans. Low levels of activity, at the initial screening concentration of 32 μg/mL, were noted with analogues of (Z)-2-(3,4-dichlorophenyl)-3-phenylacrylonitriles which made up the first two focused libraries produced. The most promising analogues possessing additional substituents on the terminal aromatic ring of the synthesised acrylonitriles. Modifications of the terminal aromatic moiety were explored through epoxide installation flowed by flow chemistry mediated ring opening aminolysis with discreet sets of amines to the corresponding amino alcohols. Three new focused libraries were developed from substituted anilines, cyclic amines, and phenyl linked heterocyclic amines. The aniline-based compounds were inactive against the bacterial and fungal lines screened. The introduction of a cyclic, such as piperidine, piperazine, or morpholine, showed >50% inhibition when evaluated at 32 μg/mL compound concentration against methicillin-resistant Staphylococcus aureus. Examination of the terminal aromatic substituent via oxirane aminolysis allowed for the synthesis of three new focused libraries of afforded amino alcohols. Aromatic substituted piperidine or piperazine switched library activity from antibacterial to anti-fungal activity with ((Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)phenyl)acrylonitrile), ((Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(4-(4-hydroxyphenyl)piperazin-1-yl)propoxy)-phenyl)acrylonitrile) and ((Z)-3-(4-(3-(4-cyclohexylpiperazin-1-yl)-2-hydroxypropoxy)-phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile) showing >95% inhibition of Cryptococcus neoformans var. grubii H99 growth at 32 μg/mL. While (Z)-3-(4-(3-(cyclohexylamino)-2-hydroxypropoxy)phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile, (S,Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(piperidin-1-yl)propoxy)phenyl)acrylonitrile, (R,Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(piperidin-1-yl)propoxy)phenyl)acrylonitrile, (Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(D-11-piperidin-1-yl)propoxy)phenyl)-acrylonitrile, and (Z)-3-(4-(3-(4-cyclohexylpiperazin-1-yl)-2-hydroxypropoxy)-phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile 32 μg/mL against Staphylococcus aureus. 相似文献
822.
823.
The implicit character of micro-structural degradation is determined by specifying the time history of crack growth caused by creep–fatigue interaction at high temperature. A dual scale micro/macro-equivalent crack growth model is used to illustrate the underlying principle of multiscaling which can be applied equally well to nano/micro. A series of dual scale models can be connected to formulate triple or quadruple scale models. Temperature and time-dependent thermo-mechanical material properties are developed to dictate the design time history of creep–fatigue cracking that can serve as the master curve for health monitoring.In contrast to the conventional procedure of problem/solution approach by specifying the time- and temperature-dependent material properties as a priori, the desired solution is then defined for a class of anticipated loadings. A scheme for matching the loading history with the damage evolution is then obtained. The results depend on the initial crack size and the extent of creep in proportion to fatigue damage. The path dependent nature of damage is demonstrated by showing the range of the pertinent parameters that control the final destruction of the material. A possible scenario of 20 yr of life span for the 38Cr2Mo2VA ultra-high strength steel is used to develop the evolution of the micro-structural degradation. Three micro/macro-parameters μ*, d* and σ* are used to exhibit the time-dependent variation of the material, geometry and load effects. They are necessary to reflect the scale transitory behavior of creep–fatigue damage. Once the algorithm is developed, the material can be tailor made to match the behavior. That is a different life span of the same material would alter the time behavior of μ*, d* and σ* and hence the micro-structural degradation history. The one-to-one correspondence of the material micro-structure degradation history with that of damage by cracking is the essence of path dependency. Numerical results and graphs are obtained to demonstrate how the inherently implicit material micro-structure parameters can be evaluated from the uniaxial bulk material properties at the macroscopic scale.The combined behavior of creep and fatigue can be exhibited by specifying the parameter ξ with reference to the initial defect size a0. Large ξ (0.90 and 0.85) gives critical crack size acr = 11–14 mm (at t < 20 yr) for a0 about 1.3 mm. For small ξ (0.05 and 0.15), there results critical acr = 6–7 mm (at t < 20 yr) for a0 about 0.7–0.8 mm. The initial crack is estimated to increase its length by an order of magnitude before triggering global to the instability. This also applies ξ ≈ 0.5 where creep interacts severely with fatigue. Fine tuning of acr and a0 can be made to meet the condition oft = 20 yr.Trade off among load, material and geometric parameters are quantified such that the optimum conditions can be determined for the desired life qualified by the initial–final defect sizes. The scenario assumed in this work is indicative of the capability of the methodology. The initial–final defect sizes can be varied by re-designing the time–temperature material specifications. To reiterate, the uniqueness of solution requires the end result to match with the initial conditions for a given problem. This basic requirement has been accomplished by the dual scale micro/macro-crack growth model for creep and fatigue. 相似文献
824.
We analyze the light-flavor particle mass spectra and show that in the region up to 1.8 GeV the Hagedorn temperature for mesons is significantly larger than for baryons, reflecting the fact that the number of baryon states grows more rapidly with the mass. We show that in dual string models the ratio of the mesonic to baryonic Hagedorn temperatures is equal to
. 相似文献
825.
高强度聚焦超声用于肿瘤治疗的研究 总被引:2,自引:0,他引:2
高强度聚焦超声(HIFU)能在短时间内使病变组织的温度升至70℃以上,导致病变组织凝固坏死,是一种具有巨大潜力的、非侵入的、有效的肿瘤治疗手段。本文对HIFU的动物试验、临床应用及治疗装置的研究情况进行了总结,分析了该技术尚存在的问题,最后展望了其应用前景。 相似文献
826.
光度法直接测定原生富铂矿及浮选精矿中痕量铂、钯的研究 总被引:4,自引:0,他引:4
报道了一个不经预分离富集 ,光度法直接测定原生富铂矿及浮选精矿中的铂、钯的方法。考察了矿样分解方法 ,测定条件的选择 ,大量铁、镍、铜等 2 0余种共存元素的干扰及消除 ,测定方法的精密度和准确度等。在 SG-1 (原生富铂矿 )和 SG98-A(浮选精矿 )样品中 ,测得铂的含量为 5.96± 0 .2 7μg/ g和 2 7.9± 0 .70 μg/ g,钯的含量为 7.71± 0 .2 5μg/ g和 3 9.2± 1 .0 0 μg/ g,结果与铅试金富集法一致。 相似文献
827.
828.
对偶余模函子()°和余反射余模 总被引:3,自引:0,他引:3
本文给出对偶余模M°的结构刻划及()°作为逆变函子的左正合性.同时引入余反射余模描述余反射余代数,由此研究余反射余代数的同调性质,证明当char(F)=0时,F[x1,...,xn]°上的Serre猜测是成立的,即F[x1,...,xn]°的有限余生成内射余模均为余自由的. 相似文献
829.
830.
双波长分光光度法测定银杏果仁中直链淀粉和支链淀粉 总被引:11,自引:0,他引:11
本文研究了以碘为显色剂,应用双波长分光光度法测定银果仁中直链淀粉和支链淀粉的含量。对显色反应和光度测定的最佳条件进行了详细的考察。根据碘-直链淀粉和碘-支链淀粉复合物的吸收光谱,选择直链淀粉的测定波长为568nm和420nm,支链淀粉的测定波长为152nm和648nm,依据回归方程可求出直链淀粉和支链淀粉的含量,直链淀粉的浓度在0-36μg/mL,支链淀粉在0-110μg/mL范围内符合比耳定律, 相似文献