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1.
A series of C(3)-cyclopropyl cephems and carbacephems has been prepared by palladium catalyzed addition of diazomethane to the corresponding C(3)-vinyl derivatives. The phenylglycyl cyclopropyl cephem derivatives exhibit better Gram-positive activity than cephalexin or cefaclor, while the aminothiazole oxime cyclopropyl cephem derivatives were not as active as the corresponding C(3)-vinyl cephems. 相似文献
2.
Stéphane Terry Ihsan Y. El-Sayed Damien Destouches Pascale Maillé Nathalie Nicolaiew Guillaume Ploussard Fannie Semprez Cynthia Pimpie Himisha Beltran Arturo Londono-Vallejo Yves Allory Alexandre de la Taille David S. Salomon Francis Vacherot 《Oncotarget》2015,6(14):11994-12008
Members of the EGF-CFC (Cripto, FRL-1, Cryptic) protein family are increasingly recognized as key mediators of cell movement and cell differentiation during vertebrate embryogenesis. The founding member of this protein family, CRIPTO, is overexpressed in various human carcinomas. Yet, the biological role of CRIPTO in this setting remains unclear. Here, we find CRIPTO expression as especially high in a subgroup of primary prostate carcinomas with poorer outcome, wherein resides cancer cell clones with mesenchymal traits. Experimental studies in PCa models showed that one notable function of CRIPTO expression in prostate carcinoma cells may be to augment PI3K/AKT and FGFR1 signaling, which promotes epithelial-mesenchymal transition and sustains a mesenchymal state. In the observed signaling events, FGFR1 appears to function parallel to AKT, and the two pathways act cooperatively to enhance migratory, invasive and transformation properties specifically in the CRIPTO overexpressing cells. Collectively, these findings suggest a novel molecular network, involving CRIPTO, AKT, and FGFR signaling, in favor of the emergence of mesenchymal-like cancer cells during the development of aggressive prostate tumors. 相似文献
3.
Swatantra Pratap Singh Karthik Rathinam Roni Kasher Christopher J. Arnusch 《RSC advances》2018,8(48):27027
Sericin, a protein waste product of the silk industry, was crosslinked with chitosan, and a chitosan–sericin conjugate (CS) was prepared, characterized and used to remove hexavalent chromium (Cr(vi)) ions and methyl orange (MO) dye from aqueous solutions. The CS was shown to effectively remove Cr(vi) ions and MO dye at maximum adsorption capacities (Langmuir) of 139 mg g−1 for Cr(vi) ions and 385 mg g−1 for MO dye. Moreover, the adsorption of both Cr(vi) ions and MO dye was highly pH dependent and varied under different experimental conditions. Cr(vi) ion and MO dye uptake by the CS was confirmed by attenuated total reflectance Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy (XPS) and energy dispersive spectrometry analysis. Additionally, XPS analysis of the Cr(vi)-loaded CS revealed that Cr(vi) was reduced to the less toxic Cr(iii). The CS was shown not only to be highly amenable to regeneration, but also to be able to effectively remove MO dye and Cr(vi) ions from a binary mixture.Sericin, a protein waste product of the silk industry, was crosslinked with chitosan, and a chitosan–sericin conjugate (CS) was prepared, characterized and used to remove hexavalent chromium (Cr(vi)) ions and methyl orange dye from aqueous solutions. 相似文献
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Eve Dubé Fannie Defay Vladimir Gilca Julie A Bettinger Chantal Sauvageau France Lavoie François D Boucher Shelly McNeil Ian Gemmill Nicole Boulianne 《BMC public health》2011,11(1):128
Background
In June 2009, the World Health Organization declared an A(H1N1) influenza pandemic. In October 2009, the largest vaccination campaign in Canadian history began. The aim of this study was to document paediatricians' knowledge, attitudes and practices (KAP) regarding A(H1N1) pandemic influenza and its prevention by vaccination just after the beginning of the A(H1N1) vaccination campaign and to compare the results with those obtained before campaign initiation. 相似文献7.
8.
The calcium-independent form of phospholipase A2 (iPLA2), an enzyme known to generate arachidonic acid (AA), was recently identified as the predominant constitutive phospholipase in the hippocampus. The present study shows that the iPLA2 inhibitor bromoenol lactone, when introduced into hippocampal CA1 pyramidal cells through a patch pipette, generated a dose-dependent increase in the amplitude of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-mediated excitatory postsynaptic currents (EPSCs). The iPLA2 inhibitor by itself interfered with neither paired pulse facilitation nor N-methyl-D-aspartate (NMDA) receptor-mediated EPSCs, suggesting that its influence on synaptic transmission is postsynaptic in origin and specific to the AMPA subtype of glutamate receptors. Comparable results were obtained with palmitoyl trifluoromethyl ketone, a second structurally distinct iPLA2 inhibitor. The ability of iPLA2 inhibitors to increase AMPA receptor-mediated currents was also reproduced by MK-866, an inhibitor recognized to interfere with the generation of 5-lipoxygenase by-products of AA. At the biochemical level, we found that AMPA, but not NMDA glutamate receptor subunits, were upregulated in rat brain sections pre-incubated with the iPLA2 inhibitors. Collectively, these results provide the first experimental evidence that constitutive iPLA2 and/or its metabolites play an important role in the postsynaptic modulation of neurotransmission in CA1 pyramidal cells of the hippocampus. 相似文献
9.
In the present study, we have investigated the viability of using tetrodotoxin (TTX) to induce selective blockade of myelinated fibre conduction in rabbit sural nerve, and explored some aspects of reflexes evoked by non-myelinated sural nerve afferents before and after application of TTX. In rabbits decerebrated under halothane-nitrous oxide anaesthesia, application of 30 nM TTX to the desheathed sural nerve completely blocked Abeta and Adelta waves of the compound action potential evoked by electrical stimulation of the nerve at 95 times threshold. The amplitude of C-fibre volleys evoked by these stimuli was reduced to a mean of 60 % of pre-treatment values. Reflexes evoked in medial gastrocnemius motoneurones by sural nerve stimulation showed corresponding changes after TTX treatment, with activation latency increasing from 5-7 ms in the control state to > 100 ms after TTX application. Temporal summation (wind up) in long latency reflexes (> 100 ms) was significantly enhanced after application of TTX. These data show that low concentrations of TTX can selectively block conduction in rabbit sural nerve A-fibres, providing a method for studying the central actions of non-myelinated C-fibres in isolation. 相似文献
10.
A beta -hairpin structure in a 13-mer peptide that binds alpha -bungarotoxin with high affinity and neutralizes its toxicity 下载免费PDF全文
Scherf T Kasher R Balass M Fridkin M Fuchs S Katchalski-Katzir E 《Proceedings of the National Academy of Sciences of the United States of America》2001,98(12):6629-6634
Snake-venom alpha-bungarotoxin is a member of the alpha-neurotoxin family that binds with very high affinity to the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction. The structure of the complex between alpha-bungarotoxin and a 13-mer peptide (WRYYESSLEPYPD) that binds the toxin with high affinity, thus inhibiting its interactions with AChR with an IC(50) of 2 nM, has been solved by (1)H-NMR spectroscopy. The bound peptide folds into a beta-hairpin structure created by two antiparallel beta-strands, which combine with the already existing triple-stranded beta-sheet of the toxin to form a five-stranded intermolecular, antiparallel beta-sheet. Peptide residues Y3(P), E5(P), and L8(P) have the highest intermolecular contact area, indicating their importance in the binding of alpha-bungarotoxin; W1(P), R2(P), and Y4(P) also contribute significantly to the binding. A large number of characteristic hydrogen bonds and electrostatic and hydrophobic interactions are observed in the complex. The high-affinity peptide exhibits inhibitory potency that is better than any known peptide derived from AChR, and is equal to that of the whole alpha-subunit of AChR. The high degree of sequence similarity between the peptide and various types of AChRs implies that the binding mode found within the complex might possibly mimic the receptor binding to the toxin. The design of the high-affinity peptide was based on our previous findings: (i) the detection of a lead peptide (MRYYESSLKSYPD) that binds alpha-bungarotoxin, using a phage-display peptide library, (ii) the information about the three-dimensional structure of alpha-bungarotoxin/lead-peptide complex, and (iii) the amino acid sequence analysis of different AChRs. 相似文献