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排序方式: 共有590条查询结果,搜索用时 15 毫秒
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Gouveia TL Frangiotti MI de Brito JM de Castro Neto EF Sakata MM Febba AC Casarini DE Amado D Cavalheiro EA Almeida SS Manchini MT Araújo RC Silva JA Naffah-Mazzacoratti Mda G 《Neurochemistry international》2012,61(1):54-62
We previously showed that patients with temporal lobe epilepsy (TLE) present an increased expression of angiotensin II (AngII) AT1 and AT2 receptors in the hippocampus, supporting the idea of an upregulation of renin-angiotensin system (RAS) in this disease. This study aimed to verify the relationship between the RAS and TLE during epileptogenesis. Levels of the peptides angiotensin I (AngI), angiotensin II (AngII) and angiotensin 1-7 (Ang 1-7), were detected by HPLC assay. Angiotensin AT1 and AT2 receptors, Mas mRNA receptors and angiotensin converting enzyme (ACE), tonin and neutral endopeptidase (NEP) mRNA were also quantified at the hippocampus of Wistar rats by real time PCR, during acute (n=10), silent (n=10) and chronic (n=10) phases of pilocarpine-induced epilepsy. We observed an increased peptide level of Ang1-7 into acute and silent phases, decreasing importantly (p≤0.05) in the chronic phase, suggesting that AngI may be converted into Ang 1-7 by NEP, which is present in high levels in these periods. Our results also showed increased peptide level of AngII in the chronic phase of this model. In contraposition, the ACE expression is reduced in all periods. These data suggest that angiotensinogen or AngI may be cleaved to AngII by tonin, which showed increased expression in all phases. We found changes in AT1, AT2 and Mas mRNA receptors levels suggesting that Ang1-7 could act at Mas receptor during the silent period. Herein, we demonstrated for the first time, changes in angiotensin-related peptides, their receptors as well as the releasing enzymes in the hippocampus of rats during pilocarpine-induced epilepsy. 相似文献
145.
Lombardo F Heckmann AB Miwa H Perry JA Yano K Hayashi M Parniske M Wang TL Downie JA 《Molecular plant-microbe interactions : MPMI》2006,19(12):1444-1450
During the symbiotic interaction between legumes and rhizobia, the host cell plasma membrane and associated plant cell wall invaginate to form a tunnel-like infection thread, a structure in which bacteria divide to reach the plant root cortex. We isolated four Lotus japonicus mutants that make infection pockets in root hairs but form very few infection threads after inoculation with Mesorhizobium loti. The few infection threads that did initiate in the mutants usually did not progress further than the root hair cell. These infection-thread deficient (itd) mutants were unaffected for early symbiotic responses such as calcium spiking, root hair deformation, and curling, as well as for the induction of cortical cell division and the arbuscular mycorrhizal symbiosis. Complementation tests and genetic mapping indicate that itd2 is allelic to Ljsym7, whereas the itdl, itd3, and itd4 mutations identified novel loci. Bacterial release into host cells did occur occasionally in the itdl, itd2, and itd3 mutants suggesting that some infections may succeed after a long period and that infection of nodule cells could occur normally if the few abnormal infection threads that were formed reached the appropriate nodule cells. 相似文献
146.
Kim KS Lu S Cornelius LA Lombardo LJ Borzilleri RM Schroeder GM Sheng C Rovnyak G Crews D Schmidt RJ Williams DK Bhide RS Traeger SC McDonnell PA Mueller L Sheriff S Newitt JA Pudzianowski AT Yang Z Wild R Lee FY Batorsky R Ryder JS Ortega-Nanos M Shen H Gottardis M Roussell DL 《Bioorganic & medicinal chemistry letters》2006,16(15):3937-3942
Synthesis and SAR of substituted pyrrolotriazine-4-one analogues as Eg5 inhibitors are described. Many of these analogues displayed potent inhibitory activities in the Eg5 ATPase and A2780 cell proliferation assays. In addition, pyrrolotriazine-4-one analogue 26 demonstrated in vivo efficacy in an iv P388 murine leukemia model. Both NMR and X-ray crystallographic studies revealed that these analogues bind to an allosteric site on the Eg5 protein. 相似文献
147.
McClure KF Letavic MA Kalgutkar AS Gabel CA Audoly L Barberia JT Braganza JF Carter D Carty TJ Cortina SR Dombroski MA Donahue KM Elliott NC Gibbons CP Jordan CK Kuperman AV Labasi JM Laliberte RE McCoy JM Naiman BM Nelson KL Nguyen HT Peese KM Sweeney FJ Taylor TJ Trebino CE Abramov YA Laird ER Volberg WA Zhou J Bach J Lombardo F 《Bioorganic & medicinal chemistry letters》2006,16(16):4339-4344
The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates. 相似文献
148.
Patricia A. McDonnell Joseph Yanchunas John A. Newitt Li Tao Susan E. Kiefer Marie Ortega Stephanie Kut Neil Burford Valentina Goldfarb Gerald J. Duke Henry Shen William Metzler Michael Doyle Zhong Chen Christine Tarby Robert Borzilleri Wayne Vaccaro Marco Gottardis Songfeng Lu Donald Crews Kyoung Kim Louis Lombardo Deborah L. Roussell 《Analytical biochemistry》2009,392(1):59-6562
Eg5 is a kinesin whose inhibition leads to cycle arrest during mitosis, making it a potential therapeutic target in cancers. Circular dichroism and isothermal titration calorimetry of our pyrrolotriazine-4-one series of inhibitors with Eg5 motor domain revealed enhanced binding in the presence of adenosine 5′-diphosphate (ADP). Using this information, we studied the interaction of this series with ADP-Eg5 complexes using a thermal shift assay. We measured up to a 7 °C increase in the thermal melting (Tm) of Eg5 for an inhibitor that produced IC50 values of 60 and 130 nM in microtubule-dependent adenosine triphosphatase (ATPase) and cell-based cytotoxicity assays, respectively. In general, the inhibitor potency of the pyrrolotriazine-4-one series in in vitro biological assays correlated with the magnitude of the thermal stability enhancement of ADP-Eg5. The thermal shift assay also confirmed direct binding of Eg5 inhibitors identified in a high-throughput screen and demonstrated that the thermal shift assay is applicable to a range of chemotypes and can be useful in evaluating both potent (nM) and relatively weakly binding (μM) leads. Overall, the thermal shift assay was found to be an excellent biophysical method for evaluating direct binding of a large number of compounds to Eg5, and it complemented the catalytic assay screens by providing an alternative determination of inhibitor potency. 相似文献
149.
F. Amato M. Cannataro C. Cosentino A. Garozzo N. Lombardo C. Manfredi F. Montefusco G. Tradigo P. Veltri 《Biomedical signal processing and control》2009,4(3):206-211
Voice is the result of the coordination of the whole pneumophonoarticulatory apparatus. The analysis of the voice allows the identification of the diseases of the vocal apparatus and currently is carried out from an expert doctor through methods based on the auditory analysis. The paper presents a web-based system for the acquisition and automatic analysis of vocal signals. Vocal signals are submitted by the users through a simple web-interface and are analyzed in real-time by using state-of-the art signal processing techniques, providing first-level information on possible voice alterations. The system offers different analysis functions to the doctors that may analyze suspected cases in detail. The system is currently being tested in the otorhinolaryngologist setting to carry out mass prevention via screening at a regional scale. 相似文献
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