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811.
Manuel Criado José Mulet Mar Castillo Susana Gerber Salvador Sala Francisco Sala 《Journal of neurochemistry》2010,112(1):103-111
Recently, we have shown that the α-helix present at the N-termini of α7 nicotinic acetylcholine receptors plays a crucial role in their biogenesis. Structural data suggest that this helix interacts with the loop linking β-strands β2 and β3 (loop 3). We studied the role of this loop as well as its interaction with the helix in membrane receptor expression. Residues from Asp62 to Val75 in loop 3 were mutated. Mutations of conserved amino acids, such as Asp62, Leu65 and Trp67 abolished membrane receptor expression in Xenopus oocytes. Others mutations, at residues Asn68, Ala69, Ser70, Tyr72, Gly74, and Val 75 were less harmful although still produced significant expression decreases. Steady state levels of wild-type and mutant α7 receptors (L65A, W67A, and Y72A) were similar but the formation of pentameric receptors was impaired in the latter (W67A). Mutation of critical residues in subunits of heteromeric nicotinic acetylcholine receptors (α3β4) also abolished their membrane expression. Complementarity between the helix and loop 3 was evidenced by studying the expression of chimeric α7 receptors in which these domains were substituted by homologous sequences from other subunits. We conclude that loop 3 and its docking to the α-helix is an important requirement for receptor assembly. 相似文献
812.
813.
Meire Nikaido Karina A. A. Tonani Fabiana C. Julião Tânia M. B. Trevilato Angela M. M. Takayanagui Sérgio M. Sanches José L. Domingo Susana I. Segura-Muñoz 《Biological trace element research》2010,134(3):342-351
The purpose of this study was to verify the effect of organic gallium on ovariectomized osteopenic rats. Thirty Wistar female rats used were divided into three groups: (1) sham-operation rats (control), (2) ovariectomized (OVX) rats with osteopenia, and (3) OVX rats with osteopenia treated with organic gallium. Treatments were performed over an 8-week period. At sacrifice, the fifth lumbar vertebral body, one tibia, one femur, and the fourth lumbar vertebrae were removed, subjected to micro-CT for determination of trabecular bone structure, and then processed for histomorphometry to assess bone turnover. The femoral neck was used for mechanical compression testing. Treatment with organic gallium increased bone volume in OVX animals. Organic gallium-treated animals had significant increases in trabecular and cortical thickness and bone strength. The plasma total calcium and inorganic phosphate concentrations in OVX rats decreased and bone mineral content in the lumbar vertebrae and femur increased after treatment with organic gallium. These data provide an important proof of concept that organic gallium may represent a powerful approach to treating or reversing severe osteoporosis in humans. 相似文献
814.
815.
Jimenez-Rojo L Ibarretxe G Aurrekoetxea M de Vega S Nakamura T Yamada Y Unda F 《Histology and histopathology》2010,25(12):1621-1630
Odontogenesis is governed by a complex network of intercellular signaling events between the dental epithelium and mesenchyme. This network leads to the progressive determination of tooth shape, and to the differentiation of these tissues into enamel-producing ameloblasts and dentin-producing odontoblasts respectively. Among the main signaling pathways involved in the regulation of tooth development, Bone Morphogenetic Protein (BMP), Sonic hedgehog (Shh) and Wingless-type MMTV integration site (Wnt) pathways have been reported to play significant roles. Recently, the phenotype of mice deficient in Epiprofin/Sp6 (Epfn) has been found to present striking dental abnormalities, including a complete lack of differentiated ameloblasts and consequently no enamel, highly altered molar cusp patterns and the formation of multiple supernumerary teeth. In this article, we review the interaction of Epfn with the BMP, Shh and Wnt pathways in the regulation of tooth development, based on the data obtained from the study of several genetically modified mice. 相似文献
816.
The Intra-Hippocampal Leucine Administration Impairs Memory Consolidation and LTP Generation in Rats
Viviane Glaser Valeria P. Carlini Laura Gabach Marisa Ghersi Susana Rubiales de Barioglio Oscar A. Ramirez Mariela F. Perez Alexandra Latini 《Cellular and molecular neurobiology》2010,30(7):1067-1075
Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder,
predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental
retardation is found in a considerable number of individuals affected by this deficieny, the mechanisms underlying the neuropathology
of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal
leucine administration in the step-down test in rats. In addition, the leucine effects on the electrophysiological parameter,
long-term potentiation generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats
were bilaterally administrated with leucine (80 nmol/hippocampus; 160 nmol/rat) or artificial cerebrospinal fluid (controls)
into the hippocampus immediately post-training in the behavioral task. Twenty-four hours after training in the step-down test,
the latency time was evaluated and afterwards animals were sacrificed for assessing the ex vivo biochemical measurements.
Leucine-treated animals showed impairment in memory consolidation and a complete inhibition of long-term potentiation generation
at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from
leucine-administered rats. These data strongly indicate that leucine compromise memory consolidation, and that impairment
of long-term potentiation generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious
leucine effect on cognition. 相似文献
817.
Renee Aspiotis Denis Deschênes Daniel Dubé Yves Girard Zheng Huang France Laliberté Susana Liu Robert Papp Donald W. Nicholson Robert N. Young 《Bioorganic & medicinal chemistry letters》2010,20(18):5502-5505
The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimization of the series led to the discovery of compound 26b, a highly potent (IC50 = 0.6 nM) and selective PDE4D inhibitor with a 75-fold selectivity over the A, B, and C subtypes and over 18,000-fold selectivity against other PDE family members. Rat pharmacokinetics and tissue distribution are also summarized. 相似文献
818.
Magnus Nilsson Anna Karin Belfrage Stefan Lindström Horst Wähling Charlotta Lindquist Susana Ayesa Pia Kahnberg Mikael Pelcman Kurt Benkestock Tatiana Agback Lotta Vrang Ylva Terelius Kristina Wikström Elizabeth Hamelink Christina Rydergård Michael Edlund Anders Eneroth Pierre Raboisson Tse-I Lin Herman de Kock Åsa Rosenquist 《Bioorganic & medicinal chemistry letters》2010,20(14):4004-4011
Novel NS3/4A protease inhibitors comprising quinazoline derivatives as P2 substituent were synthesized. High potency inhibitors displaying advantageous PK properties have been obtained through the optimization of quinazoline P2 substituents in three series exhibiting macrocyclic P2 cyclopentane dicarboxylic acid and P2 proline urea motifs. For the quinazoline moiety it was found that 8-methyl substitution in the P2 cyclopentane dicarboxylic acid series improved on the metabolic stability in human liver microsomes. By comparison, the proline urea series displayed advantageous Caco-2 permeability over the cyclopentane series. Pharmacokinetic properties in vivo were assessed in rat on selected compounds, where excellent exposure and liver-to-plasma ratios were demonstrated for a member of the 14-membered quinazoline substituted P2 proline urea series. 相似文献
819.
820.
Allan Jefferson Guimarães Susana Frases Radamés J. B. Cordero Leonardo Nimrichter Arturo Casadevall Joshua D. Nosanchuk 《Cellular microbiology》2010,12(6):740-753
The polysaccharide capsule of the fungus Cryptococcus neoformans is its main virulence factor. In this study, we determined the effects of mannitol and glucose on the capsule and exopolysaccharide production. Growth in mannitol significantly increased capsular volume compared with cultivation in glucose. However, cells grown in glucose concentrations higher than 62.5 mM produced more exopolysaccharide than cells grown in mannitol. The fibre lengths and glycosyl composition of capsular polysaccharide from yeast grown in mannitol was structurally different from that of yeast grown in glucose. Furthermore, mannitol treatment of mice infected intratracheally with C. neoformans resulted in fungal cells with significantly larger capsules and the mice had reduced fungal dissemination to the brain. Our results demonstrate the capacity of carbohydrate source and concentration to modify the expression of a major virulence factor of C. neoformans. These findings may impact the clinical management of cryptococcosis. 相似文献