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891.
Paris V. Stefanoudis Wilfredo Y. Licuanan Tiffany H. Morrison Sheena Talma Joeli Veitayaki Lucy C. Woodall 《Current biology : CB》2021,31(4):R184-R185
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892.
Tiffany C. Ho Natalie A. Horn Tuan Huynh Lucy Kelava Jeffry B. Lansman 《Channels (Austin, Tex.)》2012,6(4):246-254
We recorded the activity of single mechanosensitive (MS) ion channels from membrane patches on single muscle fibers isolated from mice. We investigated the actions of various TRP (transient receptor potential) channel blockers on MS channel activity. 2-aminoethoxydiphenyl borate (2-APB) neither inhibited nor facilitated single channel activity at submillimolar concentrations. The absence of an effect of 2-APB indicates MS channels are not composed purely of TRPC or TRPV1, 2 or 3 proteins. Exposing patches to 1-oleolyl-2-acetyl-sn-glycerol (OAG), a potent activator of TRPC channels, also had no effect on MS channel activity. In addition, flufenamic acid and spermidine had no effect on the activity of single MS channels. By contrast, SKF-96365 and ruthenium red blocked single-channel currents at micromolar concentrations. SKF-96365 produced a rapid block of the open channel current. The blocking rate depended linearly on blocker concentration, while the unblocking rate was independent of concentration, consistent with a simple model of open channel block. A fit to the concentration-dependence of block gave kon = 13 x 106 M−1s−1 and koff = 1609 sec−1 with KD = ~124 µM. Block by ruthenium red was complex, involving both reduction of the amplitude of the single-channel current and increased occupancy of subconductance levels. The reduction in current amplitude with increasing concentration of ruthenium red gave a KD = ~49 µM. The high sensitivity of MS channels to block by ruthenium red suggests MS channels in skeletal muscle contain TRPV subunits. Recordings from skeletal muscle isolated from TRPV4 knockout mice failed to show MS channel activity, consistent with a contribution of TRPV4. In addition, exposure to hypo-osmotic solutions increases opening of MS channels in muscle. Our results provide evidence TRPV4 contributes to MS channels in skeletal muscle. 相似文献
893.
Erina Vlashi Malcom Mattes Chann Lagadec Lorenza Della Donna Tiffany M Phillips Polin Nikolay William H McBride Frank Pajonk 《Translational oncology》2010,3(1):50-55
Proteasome inhibitors are emerging as a new class of cancer therapeutics, and bortezomib has shown promise in the treatment of multiple myeloma and mantle cell lymphoma. However, bortezomib has failed to have an effect in preclinical models of glioma. NPI-0052 is a new generation of proteasome inhibitors with increased potency and strong inhibition of all three catalytic activities of the 26S proteasome. In this article, we test the antitumor efficacy of NPI-0052 against glioma, as a single agent and in combination with temozolomide and radiation using five different glioma lines. The intrinsic radiation sensitivities differed for all the lines and correlated with their PTEN expression status. In vitro, NPI-0052 showed a dose-dependent toxicity, and its combination with temozolomide resulted in radiosensitization of only the cell lines with a mutated p53. The effect of NPI-0052 as a single agent on glioma xenografts in vivo was only modest in controlling tumor growth, and it failed to radiosensitize the glioma xenografts to fractionated radiation. We conclude that NPI-0052 is not a suitable drug for the treatment of malignant gliomas despite its efficacy in other cancer types. 相似文献
894.
Enav Vidan Maria Novosolov Aaron M. Bauer Fernando Castro Herrera Laurent Chirio Cristiano de Campos Nogueira Tiffany M. Doan Amir Lewin Danny Meirte Zoltan T. Nagy Daniel Pincheira‐Donoso Oliver J.S. Tallowin Omar Torres Carvajal Peter Uetz Philipp Wagner Yuezhao Wang Jonathan Belmaker Shai Meiri 《Journal of Biogeography》2019,46(10):2147-2158
895.
Deficits in behavioral sensitization and dopaminergic responses to methamphetamine in adenylyl cyclase 1/8‐deficient mice
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896.
Eleanor I. Miller Hye-Ryun K. Norris Douglas E. Rollins Stephen T. Tiffany Diana G. Wilkins 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2010,878(9-10):725-737
A novel validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) procedure was developed and fully validated for the simultaneous determination of nicotine-N-β-d-glucuronide, cotinine-N-oxide, trans-3-hydroxycotinine, norcotinine, trans-nicotine-1′-oxide, cotinine, nornicotine, nicotine, anatabine, anabasine and cotinine-N-β-d-glucuronide in human plasma or urine. Target analytes and corresponding deuterated internal standards were extracted by solid-phase extraction and analyzed by LC–MS/MS with electrospray ionization (ESI) using multiple reaction monitoring (MRM) data acquisition. Calibration curves were linear over the selected concentration ranges for each analyte, with calculated coefficients of determination (R2) of greater than 0.99. The total extraction recovery (%) was concentration dependent and ranged between 52–88% in plasma and 51–118% in urine. The limits of quantification for all analytes in plasma and urine were 1.0 ng/mL and 2.5 ng/mL, respectively, with the exception of cotinine-N-β-d-glucuronide, which was 50 ng/mL. Intra-day and inter-day imprecision were ≤14% and ≤17%, respectively. Matrix effect (%) was sufficiently minimized to ≤19% for both matrices using the described sample preparation and extraction methods. The target analytes were stable in both matrices for at least 3 freeze–thaw cycles, 24 h at room temperature, 24 h in the refrigerator (4 °C) and 1 week in the freezer (?20 °C). Reconstituted plasma and urine extracts were stable for at least 72 h storage in the liquid chromatography autosampler at 4 °C. The plasma procedure has been successfully applied in the quantitative determination of selected analytes in samples collected from nicotine-abstinent human participants as part of a pharmacokinetic study investigating biomarkers of nicotine use in plasma following controlled low dose (7 mg) transdermal nicotine delivery. Nicotine, cotinine, trans-3-hydroxycotinine and trans-nicotine-1′-oxide were detected in the particular sample presented herein. The urine procedure has been used to facilitate the monitoring of unauthorized tobacco use by clinical study participants at the time of physical examination (before enrollment) and on the pharmacokinetic study day. 相似文献
897.
György Nagy Agnes Koncz Tiffany Telarico David Fernandez Barbara Érsek Edit Buzás András Perl 《Arthritis research & therapy》2010,12(3):210
Nitric oxide (NO) has been shown to regulate T cell functions under physiological conditions, but overproduction of NO may
contribute to T lymphocyte dysfunction. NO-dependent tissue injury has been implicated in a variety of rheumatic diseases,
including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several studies reported increased endogenous
NO synthesis in both SLE and RA, and recent evidence suggests that NO contributes to T cell dysfunction in both autoimmune
diseases. The depletion of intracellular glutathione may be a key factor predisposing patients with SLE to mitochondrial dysfunction,
characterized by mitochondrial hyperpolarization, ATP depletion and predisposition to death by necrosis. Thus, changes in
glutathione metabolism may influence the effect of increased NO production in the pathogenesis of autoimmunity. 相似文献
898.
Osman Gulsen Thomas Eickhoff Tiffany Heng-Moss Robert Shearman Frederick Baxendale Gautam Sarath Donald Lee 《Arthropod-Plant Interactions》2010,4(1):45-55
Peroxidases play an important role in plant stress related interactions. This research assessed the role of peroxidases in
the defense response of resistant and susceptible buffalograsses [Buchloe dactyloides (Nutt.) Engelm] and zoysiagrasses (Zoysia japonica Steudel) to the western chinch bug, Blissus occiduus Barber. The objectives were: (1) to assess the relationships among protein content, basal peroxidase levels, chinch bug injury,
and ploidy levels of chinch bug-resistant and -susceptible buffalograsses; (2) to compare peroxidase activity levels of resistant
and susceptible buffalograsses and zoysiagrasses in response to chinch bug feeding; (3) and to analyze extracted proteins
from chinch bug-resistant and -susceptible buffalograsses and zoysiagrasses by native gel electrophoresis to obtain information
on the peroxidase profiles. Correlation analyses of 28 buffalograss genotypes with varying levels of chinch bug resistance
and ploidy levels indicated that buffalograss total protein content was correlated (r = 0.47, P = 0.01) to chinch bug injury, while basal peroxidase levels was not (r = 0.19, P = 0.29), suggesting that the up-regulation of peroxidases in resistant buffalograsses is a direct response to chinch bug
feeding. Three of the four chinch bug-resistant buffalograss genotypes evaluated had higher peroxidase activity in the infested
plants compared to control plants. Peroxidase activity levels were similar between infested and control plants of the two
highly susceptible buffalograss genotypes. Zoysiagrasses had lower peroxidase activity in general when compared to buffalograss
control plants, and only ‘Zorro’ consistently showed higher peroxidase activity in the infested plants. Native gel electrophoresis
analysis identified differences in the isozyme profiles of infested and control buffalograsses ‘Prestige’ and 196, and the
zoysiagrass ‘Zorro’. Results from this study suggest that peroxidases have the potential to be used as markers for selecting
chinch bug resistant turfgrasses, and may help explain how plants defend themselves against biotic stresses, such as chinch
bugs. 相似文献
899.
David F. Razidlo Tiffany J. Whitney Michelle E. Casper Meghan E. McGee-Lawrence Bridget A. Stensgard Xiaodong Li Frank J. Secreto Sarah K. Knutson Scott W. Hiebert Jennifer J. Westendorf 《PloS one》2010,5(7)
Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health. 相似文献
900.
Jacqueline C. Merrill Tiffany A. Melhuish Michael H. Kagey Shen-Hsi Yang Andrew D. Sharrocks David Wotton 《PloS one》2010,5(1)