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101.
Overactive and overexpressed kinases have been implicated in the cause and progression of many cancers. Kinase inhibitors offer a targeted approach for treating cancers associated with increased or deregulated kinase activity. Often, however, cancer cells exhibit initial resistance to these inhibitors or evolve to develop resistance during treatment. Additionally, cancers of any one tissue type are typically heterogeneous in their oncogenesis mechanisms, and thus diagnosis of a particular type of cancer does not necessarily provide insight into what kinase therapies may be effective. For example, while some lung cancer cells that overexpress the epidermal growth factor receptor (EFGR) respond to treatment with EGFR kinase inhibitors, overexpression or hyperactivity of Met kinase correlates with resistance to EGFR kinase inhibitors. Here we describe a microfluidic-based assay for quantifying Met kinase activity in cancer cell lysates with the eventual goals of predicting cancer cell responsiveness to kinase inhibitors and monitoring development of resistance to these inhibitors. In this assay, we immobilized a phosphorylation substrate for Met kinase into macroporous hydrogel micropillars. We then exposed the micropillars to a cancer cell lysate and detected substrate phosphorylation using a fluorescently conjugated antibody. This assay is able to quantify Met kinase activity in whole cell lysate from as few as 150 cancer cells. It can also detect cells expressing overactive Met kinase in a background of up to 75% non-cancerous cells. Additionally, the assay can quantify kinase inhibition by the Met-specific kinase inhibitors SU11274 and PHA665752, suggesting predictive capability for cellular response to kinase inhibitors. 相似文献
102.
The atomic structure of the β-SiC(100)-(2 × 1) surface was analyzed using dynamical calculations of low energy electron diffraction (LEED) intensities measured with a video camera. Surface composition was monitored using Auger electron spectroscopy (AES). The LEED calculations utilized our recently developed automated tensor LEED method. The results indicate that the surface is terminated by a monolayer of silicon with the topmost silicon atoms forming asymmetric, buckled dimers. 相似文献
103.
Kim Y. C. Powers E. J. 《IEEE transactions on plasma science. IEEE Nuclear and Plasma Sciences Society》1977,5(1):31-40
The effects of frequency averaging (i. e., data smoothing) on digitally computed plasma-wave coherence-spectra are investigated. Such averaging, or smoothing, of the data is necessary to reduce the variance of the spectral estimators to acceptable levels. However, too much averaging results in a loss of frequency resolution and in an "artificial" reduction of the degree of coherence characterizing each wave in the fluctuation spectrum. This latter problem is the subject of this paper and is concluded that in order to avoid such difficulties, it is necessary: (1) that the averaging bandwidth be small compared to the spectral bandwidth of the wave packet, and (2) that the distance between the two spatial monitoring points be small compared to the coherence length of the wave packet. 相似文献
104.
105.
We report the measurement of the strong interaction shifts and widths of the pionic 3d → 2p transitions in separated isotopes of 50,52,54Cr and natural Sc, V, Mn, and Fe. Using these new data in combination with earlier low-Z pionic data (6 ? Z ? 20) we have studied the phenomenological pion-nuclear potential. Employing nuclear structure information from measured charge densities and Hartree-Fock calculations, we have fitted the pion-nuclear potential parameters to the pionic-atom data. We have explored the sensitivity of these data to the value of the Lorentz-Lorenz parameter ξ. The addition of an isovector dependence to the s- and p-wave two-nucleon terms is shown to be unnecessary at the present level of experimental accuracy. We have used the deduced optical potentials to determine the neutron radii of the nuclei 20 ? Z ? 26 and find reasonable agreement with Hartree-Fock predictions and with the results of other hadronic probes for 20 ? Z ? 23 but poor agreement for 24 ? Z ? 26. 相似文献
106.
Ranasinghe RT Rusling DA Powers VE Fox KR Brown T 《Chemical communications (Cambridge, England)》2005,(20):2555-2557
Substituted 3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one nucleoside analogues have been synthesised from 5-alkynyl-uridine derivatives, incorporated into triplex forming oligonucleotides (TFOs) and found to selectively bind CG inversions with enhanced affinity compared to T. 相似文献
107.
A J Banes G W Link W C Beckman J L Camps S K Powers 《Journal of chromatography. A》1986,356(2):301-309
Rhodamine 123 is a fluorescent vital dye which has potential for therapeutic use in cancer treatment. The dye concentrates in mitochondria of normal and neoplastic cells but accumulates in and is toxic to neoplastic cells. When dye-treated cells are irradiated with blue laser light at 514 nm, mitochondrial injury or cell death results. Rhodamine concentration in cultured cells and tumor tissue was quantitated to correlate cell or tumor death with drug dose. A reversed-phase separation of rhodamine 123 was accomplished using a gradient of 0.05 M phosphate buffer pH 2.85 (mobile phase A) and acetonitrile (mobile phase B), 10-80% B in 15 min with a DuPont Golden Series C8 column. Effluent was monitored with a fluorescence detector at 295 nm excitation and 520 nm emission. Stock rhodamine 123 contained approximately 6-8% of rhodamine 110, the parent compound, which eluted at 9.8 min whereas rhodamine 123 eluted at 11.7 min. Structural verification of both compounds by field desorption mass spectrometry was performed. This is the first report of the chemical separation and quantitation of rhodamine 123 from cultured tumor cells or tumor tissue. 相似文献
108.
[reaction: see text] At 275 degrees C, 8-exo-methylbicyclo[4.2.0]oct-2-ene (1a) undergoes a [1,3] sigmatropic rearrangement to 5-methylbicyclo[2.2.2]oct-2-enes, of which the orbital symmetry-allowed si product is only marginally favored over the forbidden sr product; that is, si/sr is 2.4. Accompanying the [1,3] shift are significant amounts of epimerization and fragmentation. The 8-endo epimer 1b, which yields no [1,3] product, experiences primarily direct fragmentation and secondarily epimerization. A diradical intermediate can account for all such observations. 相似文献
109.
Richard J. Sundberg Rita Broome Claudia Powers Walters Dora Schnur 《Journal of heterocyclic chemistry》1981,18(4):807-809
Benzenesulfonylindole is converted to a dilithio derivative by 2.2 equivalents of lithiating reagent. The dilithio derivative gives rise to sultones on reaction with carbonyl compounds. This reaction proceeds by an intramolecular displacement of the indole group from the bis-adduct. Fair to poor yields of the 2-indolycarbinols can also be isolated. Benzoyl chloride forms a thiazine dioxide ring by addition at both the 2-indolyl and 2′-phenylsulfonyl positions. 3-Methyl-1-benzenesulfonylindole is also easily dilithiated. 相似文献
110.
Christopher M. Lemon Michael Huynh Andrew G. Maher Bryce L. Anderson Dr. Eric D. Bloch Prof. Dr. David C. Powers Prof. Dr. Daniel G. Nocera 《Angewandte Chemie (International ed. in English)》2016,55(6):2176-2180
The ground state electronic structure of copper corroles has been a topic of debate and revision since the advent of corrole chemistry. Computational studies formulate neutral Cu corroles with an antiferromagnetically coupled CuII corrole radical cation ground state. X‐ray photoelectron spectroscopy, EPR, and magnetometry support this assignment. For comparison, CuII isocorrole and [TBA][Cu(CF3)4] were studied as authentic CuII and CuIII samples, respectively. In addition, the one‐electron reduction and one‐electron oxidation processes are both ligand‐based, demonstrating that the CuII centre is retained in these derivatives. These observations underscore ligand non‐innocence in copper corrole complexes. 相似文献