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排序方式: 共有36条查询结果,搜索用时 103 毫秒
1.
Desensitization of the insulin-secreting beta cell. 总被引:2,自引:0,他引:2
In human diabetes, inherent impaired insulin secretion can be exacerbated by desensitization of the beta cell by chronic hyperglycemia. Interest in this phenomenon has generated extensive studies in genetic or experimentally induced diabetes in animals and in fully in vitro systems, with often conflicting results. In general, although chronic glucose causes decreased beta-cell response to this carbohydrate, basal response and response to alternate stimulating agents are enhanced. Glucose-stimulated insulin synthesis can be increased or decreased depending on the system studied. Using a two-compartment beta-cell model of phasic insulin secretion, a unifying hypothesis is described which can explain some of the apparent conflicting data. This hypothesis suggests that glucose-desensitization is caused by an impairment in stimulation of a hypothetical potentiator singularly responsible for: 1) some of the characteristic phases of insulin secretion; 2) basal release; 3) potentiation of non-glucose stimulators; and 4) apparent "recovery" from desensitization. Review of some of the pathways that regulate insulin secretion suggest that phosphoinositol metabolism and protein kinase-C production are regulated similarly to the theoretical potentiator and their impairment is a major contributor to glucose desensitization in the beta cell. 相似文献
2.
Lewis Grodsky 《The Western journal of medicine》1967,106(1):44-48
The unsatisfactory results of radical operations in advanced anal cancer could be bettered by earlier diagnosis of the malignant lesion. The possibility of cancer should always be kept in mind when treating any of the common chronic anal diseases. Preliminary biopsy studies should be done more frequently if suspicious lesions are present and all tissues removed during minor anorectal operations should always be examined by a pathologist. Each surgical specimen should be labeled to show the site from which it was removed. Follow-up care of the patient would be simplified if the exact site of cancer origin could be identified.A recent ten-year survey of minor anorectal surgical procedures at the University of California Medical Center showed clinically unsuspected anal cancer found in 2 per cent of cases on tissue examination by the pathologist. The cancers were generally early and of the keratinizing squamous cell and nonkeratinizing varieties. 相似文献
3.
Replication slippage may cause parallel evolution in the secondary structures of mitochondrial transfer RNAs 总被引:9,自引:4,他引:5
Presence of the dihydrouridine (D) stem in the mitochondrial cysteine tRNA
is unusually variable among lepidosaurian reptiles. Phylogenetic and
comparative analyses of cysteine tRNA gene sequences identify eight
parallel losses of the D-stem, resulting in D-arm replacement loops.
Sampling within the monophyletic Acrodonta provides no evidence for
reversal. Slipped-strand mispairing of noncontiguous repeated sequences
during replication or direct replication slippage can explain repeats
observed within cysteine tRNAs that contain a D-arm replacement loop. These
two mechanisms involving replication slippage can account for the loss of
the cysteine tRNA D-stem in several lepidosaurian lineages, and may
represent general mechanisms by which the secondary structures of
mitochondrial tRNAs are altered.
相似文献
4.
5.
The complete cDNA sequence and protein reading frame of a developmentally
regulated hemocyanin subunit in the Dungeness crab (Cancer magister) is
presented. The protein sequence is aligned with 18 potentially homologous
hemocyanin-type proteins displaying apparent sequence similarities.
Functional domains are identified, and a comparison of predicted
hydrophilicities, surface probabilities, and regional backbone
flexibilities provides evidence for a remarkable degree of structural
conservation among the proteins surveyed. Parsimony analysis of the protein
sequence alignment identifies four monophyletic groups on the arthropodan
branch of the hemocyanin gene tree: crustacean hemocyanins, insect
hexamerins, chelicerate hemocyanins, and arthropodan prophenoloxidases.
They form a monophyletic group relative to molluscan hemocyanins and
nonarthropodan tyrosinases. Arthropodan prophenoloxidases, although
functionally similar to tyrosinases, appear to belong to the arthropodan
hexamer- type hemolymph proteins as opposed to molluscan hemocyanins and
tyrosinases.
相似文献
6.
7.
A kinetic model involving synthesis of proinsulin in the rough endoplasmic reticulum, maturation through the Golgi apparatus
and granules, with conversion to insulin, is proposed to account for data on the amount of insulin and of proinsulin both
secreted during various time intervals and remaining in islets. Introducing three compartments for granules makes it possible
to account for the measurement of both hot (pulse labeled with tritiated leucine) and cold proinsulin and insulin over a period
of 21/2 hr under constant glucose. Data from islets from animals pretreated with tolbutamide are also presented and modeled.
The model is then expanded so that it can be successfully applied to available data on the effects of a period of glucose
deprivation on secretion of both hot and cold hormone. Parameters have essentially the same values, where they overlap, as
were obtained (Landahl and Grodsky, 1982Bull. math. Biol.
44, 399–410) from insulin secretion by perfused rat pancreas stimulated by a variety of temporal patterns of glucose concentration. 相似文献
8.
9.
The bovine heart mitochondrial F1-ATPase (MF1) is reversibly inhibited in the dark by 4-amino-1-octylquinaldinium (AOQ) with an I0.5 value of 48 μM. When irradiated in the presence of AOQ, MF1 is photoinactivated with an apparent Kd of 12 μM. About 1.1 mol of [3H]AOQ were incorporated per mol of MF1 on complete photoinactivation. Fractionation of a cyanogen bromide digest of MF1 photolabeled with [3H]AOQ followed by fractionation of peptic digests of partially purified cyanogen bromide fragments led to isolation of two
CNBr/peptic fragments labeled with3H. Sequence analysis of the labeled peptides revealed that one contained residues 423–441 of the β subunit. A gap in position
2 of the sequence indicates that βPhe424 is derivatized. The phenyl side-chain of this residue is part of a pocket that binds
the adenine moiety of ATP or ADP at catalytic sites. The other peptide, which was labeled to a greater extent, contained residues
342–358 of the β subunit, but in this case, no gap was found in the sequence indicating that the derivatized amino-acid side-chain
might not have survived the conditions of automatic Edman degradation. This peptide contains βTyr345, the side-chain of which
is also a component of the pocket that binds the adenine moiety of ATP or ADP to catalytic sites. However, for the reason
stated, there is no direct evidence that βTyr345 is labeled in this peptide. 相似文献
10.
Ceccarelli C Grodsky NB Ariyaratne N Colman RF Bahnson BJ 《The Journal of biological chemistry》2002,277(45):43454-43462
The crystal structure of porcine heart mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH) complexed with Mn2+ and isocitrate was solved to a resolution of 1.85 A. The enzyme was expressed in Escherichia coli, purified as a fusion protein with maltose binding protein, and cleaved with thrombin to yield homogeneous enzyme. The structure was determined by multiwavelength anomalous diffraction phasing using selenium substitution in the form of selenomethionine as the anomalous scatterer. The porcine NADP+-IDH enzyme is structurally compared with the previously solved structures of IDH from E. coli and Bacillus subtilis that share 16 and 17% identity, respectively, with the mammalian enzyme. The porcine enzyme has a protein fold similar to the bacterial IDH structures with each monomer folding into two domains. However, considerable differences exist between the bacterial and mammalian forms of IDH in regions connecting core secondary structure. Based on the alignment of sequence and structure among the porcine, E. coli, and B. subtilis IDH, a putative phosphorylation site has been identified for the mammalian enzyme. The active site, including the bound Mn2+-isocitrate complex, is highly ordered and, therefore, mechanistically informative. The consensus IDH mechanism predicts that the Mn2+-bound hydroxyl of isocitrate is deprotonated prior to its NADP+-dependent oxidation. The present crystal structure has an active site water that is well positioned to accept the proton and ultimately transfer the proton to solvent through an additional bound water. 相似文献