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961.
Kurukulasuriya R Rohde JJ Szczepankiewicz BG Basha F Lai C Jae HS Winn M Stewart KD Longenecker KL Lubben TW Ballaron SJ Sham HL von Geldern TW 《Bioorganic & medicinal chemistry letters》2006,16(24):6226-6230
A series of xanthine mimetics containing 5,5 and 5,6 heterocycle fused imidazoles were synthesized as dipeptidyl peptidase IV inhibitors. Compound 7 is potent (h-DPPIV Ki = 2 nM) and exhibits excellent selectivity and no species specificity against rat and human enzymes. The X-ray structure confirms that the binding mode of 7 to rat DPPIV is similar to the parent xanthines. 相似文献
962.
Hagens O Dubos A Abidi F Barbi G Van Zutven L Hoeltzenbein M Tommerup N Moraine C Fryns JP Chelly J van Bokhoven H Gécz J Dollfus H Ropers HH Schwartz CE de Cassia Stocco Dos Santos R Kalscheuer V Hanauer A 《Human genetics》2006,118(5):578-590
The extensive heterogeneity underlying the genetic component of mental retardation (MR) is the main cause for our limited
understanding of the aetiology of this highly prevalent condition. Hence we set out to identify genes involved in MR. We investigated
the breakpoints of two balanced X;autosome translocations in two unrelated female patients with mild/moderate MR and found
that the Xp11.2 breakpoints disrupt the novel human KIAA1202 (hKIAA1202) gene in both cases. We also identified a missense exchange in this gene, segregating with the Stocco dos Santos XLMR syndrome
in a large four-generation pedigree but absent in >1,000 control X-chromosomes. Among other phenotypic characteristics, the
affected males in this family present with severe MR, delayed or no speech, seizures and hyperactivity. Molecular studies
of hKIAA1202 determined its genomic organisation, its expression throughout the brain and the regulation of expression of its mouse homologue
during development. Transient expression of the wild-type KIAA1202 protein in HeLa cells showed partial colocalisation with
the F-actin based cytoskeleton. On the basis of its domain structure, we argue that hKIAA1202 is a new member of the APX/Shroom
protein family. Members of this family contain a PDZ and two ASD domains of unknown function and have been shown to localise
at the cytoskeleton, and play a role in neurulation, cellular architecture, actin remodelling and ion channel function. Our
results suggest that hKIAA1202 may be important in cognitive function and/or development.
Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.
O. Hagens and A. Dubos contributed equally to this work. 相似文献
963.
Qaseem Fatima Maryam Zahin Mohd Sajjad Ahmad Khan Iqbal Ahmad 《Indian journal of microbiology》2010,50(2):238-242
Effect of growing seedling, seeds and seedlings extracts from seven leguminous plants (Pisum sativum, Vigna radiata, Vigna mungo, Cajanus cajan, Lentil culinaris, Cicer arietinum and Trigonella foenum graecum) were screened for their ability to influence quorum sensing controlled pigment production in Chromobacterium violaceum indicator strains (CV12472 and CVO26). Germinating seedling and seedling extracts of only P. sativum (pea) showed inhibition of violacein production. Interestingly, the T. foenum graecum (fenugreek) seed extracts enhances the pigment production. Quorum sensing regulated swarming motility in Pseudomonas aerugionsa PAO1 was reduced by pea seedling extract while enhanced by the fenugreek seed extracts. These findings suggest that plant
metabolites of some legumes interact actively with bacterial quorum sensing and could modulate its associated functions. 相似文献
964.
Arcuri HA Apponi LH Valentini SR Durigon EL de Azevedo WF Fossey MA Rahal P de Souza FP 《Protein expression and purification》2008,62(2):146-152
The Human Respiratory Syncytial Virus (HRSV) fusion protein (F) was expressed in Escherichia coli BL21A using the pET28a vector at 37 °C. The protein was purified from the soluble fraction using affinity resin. The structural quality of the recombinant fusion protein and the estimation of its secondary structure were obtained by circular dichroism. Structural models of the fusion protein presented 46% of the helices in agreement with the spectra by circular dichroism analysis. There are only few studies that succeeded in expressing the HRSV fusion protein in bacteria. This is a report on human fusion protein expression in E. coli and structure analysis, representing a step forward in the development of fusion protein F inhibitors and the production of antibodies. 相似文献
965.
966.
Peroxidase from bitter gourd was purified by three step purification scheme; ammonium sulphate fractionation, gel filtration and affinity chromatography. The enzyme was purified 42 fold with the retention of 67% of the initial activity. The enzyme exhibited its maximum activity at pH 5.6 and 40 degrees C. The enzyme retained half of its activity even after 1 h incubation at 60 degrees C. Molecular weight of the purified glycosylated bitter gourd peroxidase determined by Sephacryl S-100 and SDS-PAGE was 43 kDa. The stokes radius, diffusion coefficient and sedimentation coefficient of the purified peroxidase were 27.3 A, 8.17 x 10(-7) cm(2)/sec and 3.74 S, respectively. K(m) for o-dianisidine and ABTS were 1.3 and 4.9 mM, respectively. The activity of the enzyme was inhibited by sulfide, azide and L-cysteine. The carbohydrate content and sulfydryl groups of the enzyme were 25% (w/w) mass of the protein and 16 mmoles/mole of the protein, respectively. 相似文献
967.
We have previously characterized an acid-unfolded (U(A)) state of Mucor miehei lipase at pH 2. The effect of 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) resulted in characterization of molten-globule (MG) like states with beta-sheet secondary structure at 15% (v/v) TFE and 6% (v/v) HFIP. alpha-Helical states accumulate at 80% (v/v) TFE and 30% (v/v) HFIP. 相似文献
968.
Submicroscopic duplications of the hydroxysteroid dehydrogenase HSD17B10 and the E3 ubiquitin ligase HUWE1 are associated with mental retardation 下载免费PDF全文
Froyen G Corbett M Vandewalle J Jarvela I Lawrence O Meldrum C Bauters M Govaerts K Vandeleur L Van Esch H Chelly J Sanlaville D van Bokhoven H Ropers HH Laumonnier F Ranieri E Schwartz CE Abidi F Tarpey PS Futreal PA Whibley A Raymond FL Stratton MR Fryns JP Scott R Peippo M Sipponen M Partington M Mowat D Field M Hackett A Marynen P Turner G Gécz J 《American journal of human genetics》2008,82(2):432-443
Submicroscopic copy-number imbalances contribute significantly to the genetic etiology of human disease. Here, we report a novel microduplication hot spot at Xp11.22 identified in six unrelated families with predominantly nonsyndromic XLMR. All duplications segregate with the disease, including the large families MRX17 and MRX31. The minimal, commonly duplicated region contains three genes: RIBC1, HSD17B10, and HUWE1. RIBC1 could be excluded on the basis of its absence of expression in the brain and because it escapes X inactivation in females. For the other genes, expression array and quantitative PCR analysis in patient cell lines compared to controls showed a significant upregulation of HSD17B10 and HUWE1 as well as several important genes in their molecular pathways. Loss-of-function mutations of HSD17B10 have previously been associated with progressive neurological disease and XLMR. The E3 ubiquitin ligase HUWE1 has been implicated in TP53-associated regulation of the neuronal cell cycle. Here, we also report segregating sequence changes of highly conserved residues in HUWE1 in three XLMR families; these changes are possibly associated with the phenotype. Our findings demonstrate that an increased gene dosage of HSD17B10, HUWE1, or both contribute to the etiology of XLMR and suggest that point mutations in HUWE1 are associated with this disease too. 相似文献
969.
Reddy KK Lefkove B Chen LB Govindarajan B Carracedo A Velasco G Carrillo CO Bhandarkar SS Owens MJ Mechta-Grigoriou F Arbiser JL 《Pigment cell & melanoma research》2008,21(4):451-456
Melanoma is a common malignancy which is poorly responsive to chemotherapy and radiation. One of the major reasons melanoma responds poorly to these modalities is constitutive expression of Akt, which protects against apoptosis. The antidepressant sertraline was found to be a potent cytotoxic agent against A375 human melanoma. To determine the mechanism by which sertraline kills melanoma cells, Western blot analysis of signaling molecules, including phosphorylated Akt, caspase 9 and phospho-p70 S6 kinase was performed. Finally, the effects of sertraline on A375 xenografts in mice were assessed. Sertaline potently inhibited the phosphorylation of Akt, and caused cell death through induction of endoplasmic reticulum in vitro. Sertraline monotherapy demonstrated activity against A375 xenografts in vivo. Akt is a major cause of resistance of melanoma to current therapy. Antidepressants are commonly used to prevent interferon-induced depression. Use of antidepressants that decrease Akt may improve the efficacy of interferon and other therapies against melanoma. Further studies are needed to elucidate whether sertraline acts as an Akt inhibitor in melanoma. 相似文献
970.
Hayton K Gaur D Liu A Takahashi J Henschen B Singh S Lambert L Furuya T Bouttenot R Doll M Nawaz F Mu J Jiang L Miller LH Wellems TE 《Cell host & microbe》2008,4(1):40-51
Some human malaria Plasmodium falciparum parasites, but not others, also cause disease in Aotus monkeys. To identify the basis for this variation, we crossed two clones that differ in Aotus nancymaae virulence and mapped inherited traits of infectivity to erythrocyte invasion by linkage analysis. A major pathway of invasion was linked to polymorphisms in a putative erythrocyte binding protein, PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent parasite. Conversely, replacements that removed these polymorphisms from PfRH5 converted a virulent progeny clone to a nonvirulent parasite. Further, a proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors. 相似文献