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481.
Schneider-Yin X Hergersberg M Goldgar DE Rüfenacht UB Schuurmans MM Puy H Deybach JC Minder EI 《Human heredity》2002,54(2):69-81
Acute intermittent porphyria (AIP) is a low-penetrant autosomal dominant disorder caused by mutations in the porphobilinogen deaminase gene (PBGD). Nearly 60% of all Swiss AIP patients carry a nonsense mutation W283X (G(7916)-->A). In France, the prevalence of W283X is <5%. To determine whether W283X was a founder mutation or originated from multiple de novo events, we studied 25 apparently unrelated W283X families and index patients, 21 of Swiss and 4 of French origins. In the absence of sufficient genealogical data to verify the ancestral background of these W283X families/patients, we identified haplotypes of seven intragenic single nucleotide polymorphisms (SNPs) in the PBGD gene as well as eight microsatellites flanking the PBGD gene covering 9.88 cM in chromosome 11. Molecular cloning and sequencing experiments were required in order to completely resolve the intragenic haplotypes in this study cohort which mainly consisted of single index patients and families with limited members. Thirteen of the 25 W283X families/patients carry a SNP haplotype [C-A-A-A-G-C-W283X-G] and 12 (including four French families) carry a [T-G-G-G-G-C-W283X-G] haplotype. A less conserved microsatellite haplotype was identified among the 25 W283X alleles which allowed us to estimate the age of the mutation. Since W283X is not explained by a methylcytosine mutation, we favor the hypothesis of a single mutational event which took place on the [T-G-G-G-G-C-G] background at approximately 40 generations or 1000 years ago. Around 550 years ago, a recombination event occurred between intron 3 and 10 of the PBGD gene which resulted in the [C-A-A-A-G-C-W283X-G] haplotype only found in a restricted region. 相似文献
482.
A soil strain of Pseudomonas sp. is able to synthesize at least two aminopeptidases exhibiting high activity in the presence of Phe-beta-NA and Ala-beta-NA as substrates. Irrespective of the used substrate, total activity of studied enzymes was strongly related to concentrations of organic components (peptone, glutamic acid, glucose) in mineral media and was the higher, the higher the concentration. Tendency of changes in total activity was similar for alanyl- and phenylalanylaminopeptidase though their response to different concentrations of organic components was different. Specific activity measured in the presence of Phe-beta-NA and Ala-beta-NA as the substrates was not strictly dependent on increasing concentrations of organic components in the media. The highest specific activity of aminopeptidase was obtained in the presence of Phe-beta-NA as a substrate on the fifth day of culture in medium containing 1% glucose. The obtained results seem to indicate the inductive character of the studied aminopeptidases. On the other hand, however, they do not exclude other regulatory mechanisms of their synthesis, including catabolic repression. 相似文献
483.
Wang J Gambhir A Hangyás-Mihályné G Murray D Golebiewska U McLaughlin S 《The Journal of biological chemistry》2002,277(37):34401-34412
A peptide corresponding to the basic (+13), unstructured effector domain of myristoylated alanine-rich C kinase substrate (MARCKS) binds strongly to membranes containing phosphatidylinositol 4,5-bisphosphate (PIP(2)). Although aromatic residues contribute to the binding, three experiments suggest the binding is driven mainly by nonspecific local electrostatic interactions. First, peptides with 13 basic residues, Lys-13 and Arg-13, bind to PIP(2)-containing vesicles with the same high affinity as the effector domain peptide. Second, removing basic residues from the effector domain peptide reduces the binding energy by an amount that correlates with the number of charges removed. Third, peptides corresponding to a basic region in GAP43 and MARCKS effector domain-like regions in other proteins (e.g. MacMARCKS, adducin, Drosophila A kinase anchor protein 200, and N-methyl-d-aspartate receptor) also bind with an energy that correlates with the number of basic residues. Kinetic measurements suggest the effector domain binds to several PIP(2). Theoretical calculations show the effector domain produces a local positive potential, even when bound to a bilayer with 33% monovalent acidic lipids, and should thus sequester PIP(2) laterally. This electrostatic sequestration was observed experimentally using a phospholipase C assay. Our results are consistent with the hypothesis that MARCKS could reversibly sequester much of the PIP(2) in the plasma membrane. 相似文献
484.
A prospective randomized trial was used to determine iron concentrations in intestinal cancer tissue and colorectum polyps.
We investigated the possible difference between the concentrations of iron, ferritin, albumin, and hemoglobin in the serum
of patients with colorectal cancer and polyps. We also determined the relationship between the iron and ferritin levels in
cancer tissue, the localization of neoplasms, and the stage of their development. The study comprises 67 patients with colorectum
cancer and 42 patients with colon and rectum polyps. The metal was determined by using the total-reflection X-ray fluorescence
(TRXRF) method. The mean concentration of iron in colorectal cancer equaled 46.1 μg/g of the tissue and was higher than in
the case of polyps (43.2 μg/g). The mean serum iron level in patients with colorectal cancer was statistically lower than
in the serum of patients with polyp and in the control group (54.5, 91.3, and 108.0 μg/g, respectively). The determined average
concentration of ferritin in the serum of patients with colorectal cancer equaled 60.4 μg/g and was statistically lower than
the level of this enzyme in the serum of patients with polyps (85.2 μg/g) and in the control group (102.0 μg/g). There was
no difference between the serum albumin and hemoglobin concentrations in patients with colorectal cancer, polyps, and the
control. There was no difference in the levels of iron and ferritin depending on the location of the neoplasm and the stage
of its development. Also, there was no difference between the concentrations of iron in the cancer tissue of malignant and
benign tumors after taking into consideration sex and age of patients. During the examination we determined significantly
higher concentrations of iron in the cancer tissue and not in the polyp. The low levels of iron in the serum of patients with
malignant tumor may increase colorectal cancer risk. 相似文献
485.
Dabrowski W Czekajlo-Kolodziej U Medrala D Giedrys-Kalemba S 《FEMS microbiology letters》2003,222(1):51-57
Recently methods based on analysis of arbitrarily amplified target sites of microorganism genomes have been extensively applied in microbiological studies. The range of their applications is limited by problems with discrimination and reproducibility resulting from lack of standardised and reliable methods of optimisation. By orthogonal-array optimisation most advantageous and optimal parameters for highly discriminatory primers (CagA2+CMVin2) were selected and efficient AP-PCR (arbitrarily primed-polymerase chain reaction) fingerprinting conditions for Pseudomonas aeruginosa isolates were set up. Stable and multiplex amplicon profiles obtained in this study revealed high level of intraspecies DNA polymorphism among 20 analysed clinical strains of P. aeruginosa proving optimised AP-PCR fingerprinting to be useful in epidemiological typing of the species. 相似文献
486.
The cyclic AMP receptor protein (CRP) regulates the expression of many genes in Escherichia coli. The protein is a homodimer, and each monomer is folded into two distinct structural domains. In this study, we have used differential scanning calorimetry (DSC) and circular dichroism (CD) to measure the enthalpy change and melting temperature of the apo-CRP and CRP complexes with cAMP or DNA sequences lac, gal, and palindromic ICAP. DSC and CD measurements showed irreversible thermal denaturation process of CRP. Enthalpy of dissociation of the protein–DNA complex, as measured by DSC, depends on the DNA sequence. The thermal transition of the protein in CRP-DNA complexes, measured by CD, indicates that the protein stability in the complex is also DNA sequence-dependent. 相似文献
487.
In order to elucidate differences observed in the aggregation kinetics of hen-egg white lysozyme under crystallization conditions we have undertaken a comparative study of the enzyme marketed by Seikagaku and Sigma companies. When the crystallization of the two lysozyme preparations is followed by time-resolved dynamic light scattering, the structural differences are also observed under native conditions in the early nucleation kinetics. The differences are manifested in the formation rates of macroscopic crystals, but do not influence the morphology of the typical tetragonal lysozyme crystal. Using two-dimensional NMR we have followed the differences in the native-like solution structure of the two preparations, while the primary sequence and molecular mass are identical. According to the published structure of tetragonal lysozyme crystal the largest deviations were found for the residues involved in the intermolecular interactions in crystal structure. 相似文献
488.
The basic scaffold of most cells is afforded by the cytoskeleton (comprising microfilaments, intermediate filaments and the microtubules). The conventional methods of electron microscopy fail to visualize filamentous cell structure. They can show only these filaments lying at the section surface. Heavy metal staining (I), and the optical properties of the resins used for embedding are similar to those of proteins hence most proteinaceous structures remain unresolved and the cytoplasm seems to be quite homogenous (II). Aldehyde fixation could cross-link proteins and lead to the emergence of artificial structures (III). These limitations may be overcome by the use of the embedment-free electron microscopy (EF-EM). This technique present cellular scaffold as a purified, isolated, three-dimensional network with various thickness of filaments. Our study on the dynamic aspect of cellular scaffold indicate that the thickness and arrangement of filaments depend on cell type and both physiological or pathological environments. Thank also to the adaptation of immunocytochemistry to EF-EM it was possible to understand the nuclear matrix and cytomatrix structure in relation to function. Thus, combination these methods revealed findings suggesting the nuclear homing of proapoptotic proteins and their association with intermediate filaments. 相似文献
489.
Kozik EU Nowak R Kłosińska U Górecka K Krzyzanowska D Górecki R 《Journal of applied genetics》2002,43(1):49-53
The aim of this study was to evaluate phenotypic variation of R0 androgenic plants obtained from four seed sources and donor plants by anther culture. Several morphological traits (leaf size, petiole length, leaf division, cortex colour) and the range of diversity were evaluated. There was large variation in all traits among the donor varieties. Especially leaf division and cortex colour differed significantly among the androgenic plants that came from different seed sources. The plants regenerated from four donor plants of variety 62 were significantly different in most traits except for leaf width and cortex colour. Evaluation of R1 plants will demonstrate whether the R0 variation observed is due to genetic variation or physiological differences from tissue culture. 相似文献
490.
pSM19035 of the pathogenic bacterium Streptococcus pyogenes is a low-copy-number plasmid carrying erythromycin resistance, stably maintained in a broad range of gram-positive bacteria. We show here that the omega-epsilon-zeta operon of this plasmid constitutes a novel proteic plasmid addiction system in which the epsilon and zeta genes encode an antitoxin and toxin, respectively, while omega plays an autoregulatory function. Expression of toxin Zeta is bactericidal for the gram-positive Bacillus subtilis and bacteriostatic for the gram-negative Escherichia coli. The toxic effects of zeta gene expression in both bacterial species are counteracted by proper expression of epsilon. The epsilon-zeta toxin-antitoxin cassette stabilizes plasmids in E. coli less efficiently than in B. subtilis. 相似文献