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71.
72.
Mike De Vrieze Dieter Verzele Roman Szucs Pat Sandra Frédéric Lynen 《Analytical and bioanalytical chemistry》2014,406(25):6179-6188
Over the past decades, several in vitro methods have been tested for their ability to predict drug penetration across the blood-brain barrier. So far, in high-performance liquid chromatography, most attention has been paid to micellar liquid chromatography and immobilized artificial membrane (IAM) LC. IAMLC has been described as a viable approach, since the stationary phase emulates the lipid environment of a cell membrane. However, research in IAMLC has almost exclusively been limited to phosphatidylcholine (PC)-based stationary phases, even though PC is only one of the lipids present in cell membranes. In this article, sphingomyelin and cholester stationary phases have been tested for the first time towards their ability to predict drug penetration across the blood-brain barrier. Upon comparison with the PC stationary phase, the sphingomyelin- and cholester-based columns depict similar predictive performance. Combining data from the different stationary phases did not lead to improvements of the models. Figure
Schematic representation of how IAM-LC is used to predict drug penetration across the blood-brain barrier. 相似文献
73.
Tobias G. Brevé Mike Filius Sven Weerdenburg Stefan J. van der Griend Tim P. Groeneveld Dr. Antonia G. Denkova Dr. Rienk Eelkema 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(10):e202103523
Stimuli-responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis-azide crosslinkers that are used to prepare transparent self-supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π-extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein-loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov-triggered release is as yet inconclusive due to unexpected side-reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release. 相似文献
74.
Peleyeju Moses G. Mgedle Nande Viljoen Elvera L. Scurrel Mike S. Ray Sekhar C. 《Research on Chemical Intermediates》2021,47(10):4213-4226
Research on Chemical Intermediates - The application of microwave energy in the synthesis of catalytic materials has been indicated to induce desirable effects that lead to improved activity.... 相似文献
75.
Stefan Sander Dr. Robert Müller Dr. Mike Ahrens Prof. Dr. Martin Kaupp Prof. Dr. Thomas Braun 《Chemistry (Weinheim an der Bergstrasse, Germany)》2021,27(57):14287-14298
The reaction of [PtCl2(COD)] (COD=1,5-cyclooctadiene) with diisopropyl-2-(3-methyl)indolylphosphine (iPr2P(C9H8N)) led to the formation of the platinum(ii ) chlorido complexes, cis-[PtCl2{iPr2P(C9H8N)}2] ( 1 ) and trans-[PtCl2{iPr2P(C9H8N)}2] ( 2 ). The cis-complex 1 reacted with NEt3 yielding the complex cis-[PtCl{κ2-(P,N)-iPr2P(C9H7N)}{iPr2P(C9H8N)}] ( 3 ) bearing a cyclometalated κ2-(P,N)-phosphine ligand, while the isomer 2 with a trans-configuration did not show any reactivity towards NEt3. Treatment of 1 or 3 with (CH3)4NF (TMAF) resulted in the formation of the twofold cyclometalated complex cis-[Pt{κ2-(P,N)-iPr2P(C9H7N)}2] ( 4 ). The molecular structures of the complexes 1–4 were determined by single-crystal X-ray diffraction. The fluorido complex cis-[PtF{κ2-(P,N)-iPr2P(C9H7N)}{iPr2P(C9H8N)}] ⋅ (HF)4 ( 5 ⋅ (HF)4) was formed when complex 4 was treated with different hydrogen fluoride sources. The Pt(ii ) fluorido complex 5 ⋅ (HF)4 exhibits intramolecular hydrogen bonding in its outer coordination sphere between the fluorido ligand and the NH group of the 3-methylindolyl moiety. In contrast to its chlorido analogue 3 , complex 5 ⋅ (HF)4 reacted with CO or the ynamide 1-(2-phenylethynyl)-2-pyrrolidinone to yield the complexes trans-[Pt(CO){κ2-(P,C)-iPr2P(C9H7NCO)}{iPr2P(C9H8N)}][F(HF)4] ( 7 ) and a complex, which we suggest to be cis-[Pt{C=C(Ph)OCN(C3H6)}{κ2-(P,N)-iPr2P(C9H7N)}{iPr2P(C9H8N)}][F(HF)4] ( 9 ), respectively. The structure of 9 was assigned on the basis of DFT calculations as well as NMR and IR data. Hydrogen bonding of HF and NH to fluoride was proven to be crucial for the existence of 7 and 9 . 相似文献
76.
Chemical Probing of the Human Sirtuin 5 Active Site Reveals Its Substrate Acyl Specificity and Peptide‐Based Inhibitors 下载免费PDF全文
Claudia Roessler Theresa Nowak Martin Pannek Dr. Melanie Gertz Giang T. T. Nguyen Michael Scharfe Dr. Ilona Born Prof. Dr. Wolfgang Sippl Prof. Dr. Clemens Steegborn Prof. Dr. Mike Schutkowski 《Angewandte Chemie (International ed. in English)》2014,53(40):10728-10732
Sirtuins are NAD+‐dependent deacetylases acting as sensors in metabolic pathways and stress response. In mammals there are seven isoforms. The mitochondrial sirtuin 5 is a weak deacetylase but a very efficient demalonylase and desuccinylase; however, its substrate acyl specificity has not been systematically analyzed. Herein, we investigated a carbamoyl phosphate synthetase 1 derived peptide substrate and modified the lysine side chain systematically to determine the acyl specificity of Sirt5. From that point we designed six potent peptide‐based inhibitors that interact with the NAD+ binding pocket. To characterize the interaction details causing the different substrate and inhibition properties we report several X‐ray crystal structures of Sirt5 complexed with these peptides. Our results reveal the Sirt5 acyl selectivity and its molecular basis and enable the design of inhibitors for Sirt5. 相似文献
77.
Mike Engelhardt 《电子产品世界》2007,(1):156-157
关于LTspice/SwitcherCAD Ⅲ LTspice/SwitcherCAD Ⅲ是一款具集成原理图捕获能力的强大SPICE仿真工具. 相似文献
78.
A sequence of random variables X0,X1, … with values in {0, 1, …, n} representing a general finite-state stochastic process with absorbing state 0 is said to be directionally biased towards 0, if, for all j > 0, ϵj: = infk>0 {j − E[Xk | Xk−1 = j]} > 0. For such sequences, let t be the expected value of the time to absorption at 0. For a fixed set of biases, the least upper bound for this time can be computed with an algorithm requiring O(n2) steps. Simple upper bounds are described. In particular, t ≤ E[bx0], where bi = Σj≤i 1/¯ϵj and ¯ϵj = minl≥j {ϵl}. If all ϵj ≤ ϵj + 1 (so ¯ϵj = ϵj) and ϵn < 1, this bound for t is the best possible. For certain finite stochastic processes which we term conditionally independent of X0 = i, b(i) bounds the expected time given X0 = i. Similar results are given for lower bounds. The results of this paper were designed to be a useful tool for determining rates of convergence of stochastic optimization algorithms. © 1996 John Wiley & Sons, Inc. 相似文献
79.
In a WAG process (Water Alternate Gas), water and a miscible solvent (gas) are injected into a reservoir containing water and oil. The solvent will finger through the oil, leading to early breakthrough and poor recovery. Compared with a miscible flood, when only solvent is injected, fingering is supressed by the simultaneous injection of water, since this reduces the apparent mobility contrast between the injected and displaced fluids. The fingering in a miscible flood, with only hydrocarbon flowing, can be modelled successfully using a Todd and Longstaff fractional flow. In this paper, we demonstrate how to modify the effective Todd and Longstaff mobility ratio self-consistently to account for fingering in three component systems. The resultant empirical equations of flow are solved exactly in one dimension and are in excellent agreement with the averaged saturation and concentration profiles computed using two dimensional high resolution simulation, for a variety of injected water saturations, in both secondary and tertiary displacements. 相似文献
80.
Jeffrey Beck Richard Scritchfield Billy Sullivan Jamie Teherani Chang-Feng Wan Mike Kinch Martha Ohlson Mark Skokan Lewis Wood Pradip Mitra Mike Goodwin Jim Robinson 《Journal of Electronic Materials》2009,38(8):1579-1592
The operation of the mid-wave infrared (MWIR) HgCdTe cylindrical electron injection avalanche photodiode (e-APD) is described.
The measured gain and excess noise factor are related to the collection region fill factor. A two-dimensional diffusion model
calculates the time-dependent response and steady-state pixel point spread function for cylindrical diodes, and predicts bandwidths
near 1 GHz for small geometries. A 2 μm diameter spot scan system was developed for point spread function and crosstalk measurements at 80 K. An electron diffusion
length of 13.4 μm was extracted from spot scan data. Bandwidth data are shown that indicate bandwidths in excess of 300 MHz for small unit
cells geometries. Dark current data, at high gain levels, indicate an effective gain normalized dark density count as low
as 1000 counts/μs/cm2 at an APD gain of 444. A junction doping profile was determined from capacitance–voltage data. Spectral response data shows
a gain-independent characteristic. 相似文献