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81.
RR Lew 《Fungal genetics and biology : FG & B》1998,24(1-2):69-76
Ion channel mapping techniques are described and the results for two fungal organisms, Saprolegnia ferax and Neurospora crassa, are presented. In these species, two channel types have been characterized, stretch-activated channels exhibiting significant calcium permeability and spontaneous channels having significant potassium permeability. Two distinct analyses of patch clamp data, analysis of channel self-clustering and association between different channel types, and localization along the hyphae, reveal significant differences between the two organisms. S. ferax maintains a tip-high gradient of both channel types which is lost after disruption of the actin cytoskeleton. There is significant self-clustering of the channels, as well as interactions between channel types. N. crassa on the other hand does not maintain tip-high gradients, and clustered distributions are observed only for the stretch-activated channels. In terms of physiological roles, evidence is quite strong that the stretch-activated channels function as a growth sensor in S. ferax, but have an unknown function in N. crassa. In both organisms, the potassium permeable channels presumably function in potassium uptake. The differences between these two organisms may be due, in part, to differences in their normal environment: aquatic versus terrestrial. Copyright 1998 Academic Press. 相似文献
82.
W Rode Z Zieliński J M Dzik T Kulikowski M Bretner B Kierdaszuk J Cie?la D Shugar 《Biochemistry》1990,29(48):10835-10842
N4-Hydroxy-dCMP (N4-OH-dCMP), N4-methoxy-dCMP (N4-OMe-dCMP), and their 5-fluoro congeners (syntheses of which are described) were all slow-binding inhibitors of Ehrlich carcinoma thymidylate synthase (TS), competitive with respect to dUMP, and had differing kinetic constants describing interactions with the two TS binding sites. N4-OH-dCMP was not a substrate (no dihydrofolate produced; no tritium released with 5-3H-labeled molecule), and its inactivation of TS was methylenetetrahydrofolate-dependent, hence mechanism-based, with arrest of a step posterior to addition of cofactor and blocking abstraction of the C(5) hydrogen. Ki values for N4-OH-dCMP and its 5-fluoro analogue were in the range 10(-7) - 10(-8) M, 2-3 orders of magnitude higher for the corresponding N4-OMe analogues. The 5-methyl analogue of N4-OH-dCMP was 10(4)-fold less potent, pointing to the anti rotamer of the imino form of exocyclic N4-OH, relative to the ring N(3), as the active species. This is consistent with weaker slow-binding inhibition of the altered enzyme from 5-FdUrd-resistant, relative to parent, L1210 cells by both FdUMP and N4-OH-dCMP, suggesting interaction of both N4-OH and C(5)-F groups with the same region of the active center. Kinetic studies with purified enzyme from five sources, viz., Ehrlich carcinoma, L1210 parental, and 5-FdUrd-resistant cells, regenerating rat liver, and the tapeworm Hymenolepis diminuta, demonstrated that addition of a 5-fluoro substituent to N4-OH-dCMP increased its affinity from 2- to 20-fold for the enzyme from different sources.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
83.
de Carvalho AF da Silva Bellucco FT Kulikowski LD Toralles MB Melaragno MI 《Human genetics》2008,124(4):387-392
A family with six alive patients with partial monosomy 5p and five with partial trisomy 5p due to a t(5;15)(p13.3;p12) translocation
is reported. The translocation was present in four generations with eight balanced carriers. This is the first molecular-cytogenetic
and clinical study with both syndromes present in the same family. Using fluorescence in situ hybridization (FISH) with bacterial
artificial chromosome (BAC) probes, the breakpoint was mapped to 5p13.3, in the interval corresponding to the BAC clone RP11-1079N14,
thereof resulting a 5pter-5p13.3 deletion or duplication of ~32 Mb. These chromosome imbalances can be considered pure, since
the other imbalance produced involving chromosome 15p has no phenotypic effect. The presence of several individuals with 5p
monosomy and 5p trisomy in the same family is valuable for a better delineation of both syndromes. 相似文献
84.
Bretner M Schalinski S Borowski P Kulikowski T 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):1531-1533
Synthesis and interactions of guanosine, inosine and ribavirin 5'-fluorosulfonylbenzoyl esters with hepatitis C virus (HCV) and Flaviviruses NTPase/helicase and polymerase are described. 相似文献
85.
Terlikowski S Lenczewski A Famulski W Sulkowska M Dobrzycka B Stasiuk-Barmuta A Kulikowski M 《Folia histochemica et cytobiologica / Polish Academy of Sciences, Polish Histochemical and Cytochemical Society》2001,39(Z2):195-196
The p53, a tumour suppressor gene, is the most commonly mutated gene human cancer. In this study, we performed immunohistochemical investigations of the expression of p53 protein in hyperplastic endometrium and adenocarcinoma. Positive immunostaining was detected in 7 (30%) cases of invasive adenocarcinoma, 2 (12%) cases of simple hyperplasia with atypia and 2 (14%) cases of complex hyperplasia with atypia. In simple and complex hyperplasia without atypia staining was seen in occasional cells. The results suggested that endometrial hyperplasia is not always accompanied by p53 protein accumulation, hence its expression is not an early exponent of the neoplastic process. 相似文献
86.
Poznański J Felczak K Bretner M Kulikowski T Remin M 《Biochemical and biophysical research communications》2001,283(5):1142-1149
Although alpha-nucleosides are not found in nucleic acid, they do occur as constituents of smaller molecules in living cells, e.g., in vitamin B(12). There are now several examples of alpha-nucleosides exerting a biological activity in some instances equal to, or even exceeding, that of the corresponding beta-anomer. Examples include growth inhibitory properties against mouse leukemia cells and antitumor activity. From stereochemical point of view, alpha-anomers serve as references for studying of interaction of the base with the sugar moiety in beta-anomers and may help in better understanding of structure-activity relationships. One important problem preventing conformational analysis of alpha nucleosides is uncertainty in the determination of vicinal coupling constants from simulation of overlapping sugar proton resonances of strongly coupled spin systems. A successful resolution of near-isochronous H3' and H4' resonances made possible a full conformational analysis for a series of alpha-anomers C5-substituted 2'-deoxyuridines, including methyl, ethyl, isopropyl, fluor, vinyl, and bromovinyl, in comparison to their beta counterparts. Conformation of the sugar ring is determined from proton-proton coupling constants and described in terms of pseudorotation between two main puckering domains C2'endo (S) and C3'endo (N). A thorough analysis of chemical shifts as well as conformation of the sugar ring and C4'-C5' rotamers made possible determination of conformational preferences in equilibrium about the glycosidic bond between two regions, anti and syn. This work provides insights into the role of anomeric configuration of the base in conformational behavior of the sugar moiety, a link in the backbone of nucleic acids. 相似文献
87.
Cytogenetic instability of dental pulp stem cell lines 总被引:1,自引:0,他引:1
Duailibi MT Kulikowski LD Duailibi SE Lipay MV Melaragno MI Ferreira LM Vacanti JP Yelick PC 《Journal of molecular histology》2012,43(1):89-94
Human adult stem cells (hASCs) offer a potentially renewable source of cell types that are easily isolated and rapidly expanded
for use in regenerative medicine and cell therapies without the complicating ethical problems that are associated with embryonic
stem cells. However, the eventual therapeutic use of hASCs requires that these cells and their derivatives maintain their
genomic stability. There is currently a lack of systematic studies that are aimed at characterising aberrant chromosomal changes
in cultured ASCs over time. However, the presence of mosaicism and accumulation of karyotypic abnormalities within cultured
cell subpopulations have been reported. To investigate cytogenetic integrity of cultured human dental stem cell (hDSC) lines,
we analysed four expanded hDSC cultures using classical G banding and fluorescent in situ hybridisation (FISH) with X chromosome
specific probe. Our preliminary results revealed that about 70% of the cells exhibited karyotypic abnormalities including
polyploidy, aneuploidy and ring chromosomes. The heterogeneous spectrum of abnormalities indicates a high frequency of chromosomal
mutations that continuously arise upon extended culture. These findings emphasise the need for the careful analysis of the
cytogenetic stability of cultured hDSCs before they can be used in clinical therapies. 相似文献
88.
89.
O Stoyanov A Kister I Gelfand C Kulikowski C Chothia 《Journal of computational biology》2000,7(5):673-684
A previously developed algorithmic method for identifying a geometric invariant of protein structures, termed geometrical core, is extended to the C(L) and C(H1) domains of immunoglobulin molecules. The method uses the matrix of C(alpha) - C(alpha) distances and does not require the usual superposition of structures. The result of applying the algorithm to 53 Immunoglobulin structures led to the identification of two geometrical core sets of C(alpha) atom positions for the C(L) and C(H1) domains. 相似文献
90.
Molecular evolution of olfactomedin 总被引:2,自引:0,他引:2
Olfactomedin is a secreted polymeric glycoprotein of unknown function,
originally discovered at the mucociliary surface of the amphibian olfactory
neuroepithelium and subsequently found throughout the mammalian brain. As a
first step toward elucidating the function of olfactomedin, its
phylogenetic history was examined to identify conserved structural motifs.
Such conserved motifs may have functional significance and provide targets
for future mutagenesis studies aimed at establishing the function of this
protein. Previous studies revealed 33% amino acid sequence identity between
rat and frog olfactomedins in their carboxyl terminal segments. Further
analysis, however, reveals more extensive homologies throughout the
molecule. Despite significant sequence divergence, cysteines essential for
homopolymer formation such as the CXC motif near the amino terminus are
conserved, as is the characteristic glycosylation pattern, suggesting that
these posttranslational modifications are essential for function.
Furthermore, evolutionary analysis of a region of 53 amino acids of fish,
frog, rat, mouse, and human olfactomedins indicates that an ancestral
olfactomedin gene arose before the evolution of terrestrial vertebrates and
evolved independently in teleost, amphibian, and mammalian lineages.
Indeed, a distant olfactomedin homolog was identified in Caenorhabditis
elegans. Although the amino acid sequence of this invertebrate protein is
longer and highly divergent compared with its vertebrate homologs, the
protein from C. elegans shows remarkable similarities in terms of conserved
motifs and posttranslational modification sites. Six universally conserved
motifs were identified, and five of these are clustered in the carboxyl
terminal half of the protein. Sequence comparisons indicate that evolution
of the N-terminal half of the molecule involved extensive insertions and
deletions; the C-terminal segment evolved mostly through point mutations,
at least during vertebrate evolution. The widespread occurrence of
olfactomedin among vertebrates and invertebrates underscores the notion
that this protein has a function of universal importance. Furthermore,
extensive modification of its N-terminal half and the acquisition of a
C-terminal SDEL endoplasmic-reticulum- targeting sequence may have enabled
olfactomedin to adopt new functions in the mammalian central nervous
system.
相似文献