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131.
Bjorn?WH?van Heumen Hennie?MJ?Roelofs René?HM?te Morsche Fokko?M?Nagengast Wilbert?HM?PetersEmail author 《Orphanet journal of rare diseases》2013,8(1):181
Background
Familial adenomatous polyposis (FAP) is a disease characterized by the development of hundreds to thousands of adenomatous polyps in the colorectum early in life. Virtually all patients with FAP will develop colorectal cancer before the age of 40 to 50 years, unless prophylactic colectomy is performed, which significantly improves their prognosis. The mortality pattern has changed and duodenal cancer now is one of the main cancer-related causes of death in these patients. Practically all patients with FAP develop premalignant duodenal adenomas, which may develop to duodenal cancer in approximately 3-7% of patients. Duodenal cancer in patients with FAP has a poor prognosis. The clinical challenge is to identify patients at high-risk for duodenal carcinoma. Chemoprevention would be desirable to avoid duodenectomy. The main goal of this study is to identify risk markers in normal duodenal mucosa of patients with FAP, that could help identify patients at increased risk for malignant transformation.Methods
Messenger RNA (mRNA) levels of glutathione S-transferase A1 (GSTA1), glutathione S-transferase P1 (GSTP1), KIAA1199, E-cadherin, peroxisome proliferative activated receptor δ (PPARδ), caspase-3, cyclin D1, β-catenin, and cyclooxygenase-2 (COX-2) were measured in duodenal mucosa, using the QuantiGene 2.0 Plex assay. Levels in normal appearing mucosa of patients with FAP (n?=?37) were compared with levels in non-FAP patient controls (n?=?16). In addition, levels before and after treatment with either celecoxib & ursodeoxycholic acid (UDCA, n?=?14) or celecoxib & placebo (n?=?13) were evaluated in patients with FAP.Results
mRNA levels of glutathione S-transferase A1 (28.16% vs. 38.24%, p?=?0.008) and caspase-3 (3.30% vs. 5.31%, p?=?0.001) were significantly lower in patients with FAP vs. non-FAP patient controls, respectively. COX-2 mRNA levels in normal duodenal mucosa of patients with FAP were found to be unexpectedly low. None of the potential risk markers was influenced by celecoxib or celecoxib & UDCA.Conclusions
Protection against toxins and carcinogens (GSTA1) and apoptosis (caspase-3) is low in patients with FAP, which could contribute to increased susceptibility for malignant transformation of duodenal mucosa.Trial registration
http://ClinicalTrials.gov number NCT00808743132.
Rogers AR; Fraley AE; Bamshad MJ; Watkins WS; Jorde LB 《Molecular biology and evolution》1996,13(7):895-902
Mismatch distributions are histograms showing the pattern of nucleotide (or
restriction) site differences between pairs of individuals in a sample.
They can be used to test hypotheses about the history of population size
and subdivision (if selective neutrality is assumed) or about selection (if
a constant population size is assumed). Previous work has assumed that
mutations never strike the same site twice, an assumption that is called
the model of infinite sites. Fortunately, the results are surprisingly
robust even when this assumption is violated. We show here that (1)
confidence regions inferred using the infinite- sites model differ little
from those inferred using a model of finite sites with uniform
site-specific mutation rates, and (2) even when site- specific mutation
rates follow a gamma distribution, confidence regions are little changed
until the gamma shape parameter falls well below its plausible range, to
roughly 0.01. In addition, we evaluate and reject the proposition that
mismatch waves are produced by pooling data from several subdivisions of a
structured population.
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133.
134.
Summary Several strains of Lactococcus lactis subsp. lactis var. diacetylactis and Leuconostoc spp. were compared for product formation from citrate in milk cultures. Most strains produced acetoin and butanediol. Some strains derived from buffer starter cultures produced, in addition, -acetolactate. Lactococcus lactis strain C17, which produced acetoin and butanediol but no -acetolactate in culture, was compared physiologically with L. lactis strain Ru4, which produced only -acetolactate. Activities of enzymes involved in citrate metabolism were almost identical in both strains, with the exception of -acetolactate decarboxylase, which was missing in strain Ru4. The formation of -acetolactate, acetoin and diacetyl was further analysed in cell-free extracts. -Acetolactate synthase activity saturated at a high pyruvate concentration (100 mm). This is in agreement with the observed accumulation of pyruvate externally, and probably internally, during -acetolactate, acetoin and butanediol production by L. lactis cells.Correspondence to: J. Hugenholtz 相似文献
135.
A phylogenetic survey using the polymerase chain reaction (PCR) has
identified four major P element subfamilies in the saltans and willistoni
species groups of Drosophila. One subfamily, containing about half of the
sequences studied, consists of elements that are very similar to the
canonical (and active) P element from D. melanogaster. Within this
subfamily, nucleotide sequence differentiation among different copies from
the same species and among elements from different species is relatively
low. This observation suggests that the canonical elements are relatively
recent additions to the genome or, less likely, are evolving slowly
relative to the other subfamilies. Elements belonging to the three
noncanonical lineages are distinct from the canonical elements and from one
another. Furthermore, there is considerably more sequence variation, on the
average, within the noncanonical subfamilies compared to the canonical
elements. Horizontal transfer and the coexistence of multiple,
independently evolving element subfamilies in the same genome may explain
the distribution of P elements in the saltans and willistoni species
groups. Such explanations are not mutually exclusive, and each may be
involved to varying degrees in the maintenance of P elements in natural
populations of Drosophila.
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136.
Cytochemical demonstration of hydrogen peroxide in polymorphonuclear leukocyte phagosomes 总被引:7,自引:1,他引:6
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Phagocytosis by polymorphonuclear leukocytes (PMN) is accompanied by specific morphological and metabolic events which may result in the killing of internalized micro-organism. Hydrogen peroxide is produced in increased amounts during phagocytosis (17) and in combination with myeloperoxidase and halide ions constitute a potent, microbicidal mechanism (8,9,11). There can be direct iodination of micro-organisms (10), or alternatively, other intermediate reaction products, i.e. chloramines and aldehydes (21), can exert a microbicidal effect. The H2O2-peroxidase-halide system is presumed to operate within the phagocytic vacuole (12,18). Myeloperoxidase, present in the primary granules of PMN, enters the phagocytic vacuole during degranulation (1,4,7), and halide ions are probably derived from the extracellular medium or are present in the PMN (see 11, 18). For the operation of this system in intact cells, the presence of H2O2 in the phagocytic vacuole is necessary, and indeed this has been suggested by the work of several investigators (12, 18, 21). In the present investigation, the diaminobenzidine reaction of Graham and Karnovsky (5), modified to utilize endogenous myeloperoxidase and hydrogen peroxide, has been applied to actively phagocytizing PMN to demonstrate cytochemically the presence of H2O2 in the phagocytic vacuole. 相似文献
137.
Assembly of storage protein oligomers in the endoplasmic reticulum and processing of the polypeptides in the protein bodies of developing pea cotyledons 总被引:26,自引:0,他引:26
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Cotyledons of developing pea seeds (pisum sativum L.) were labeled with radioactive amino acids and glucosamine, and extracts were prepared and separated into fractions rich in endoplasmic reticulum (ER) or protein bodies, The time-course of synthesis of the polypeptides of legumin and vicilin and the site of their assembly into protein oligomers were studied using immunoaffinity gels and sucrose density gradients. When cotyledons were pulse-labeled (1-2 h), newly synthesized vicilin was present as a series of polypeptides with M(r) 60,000-65,000, and newly synthesized vicilin was present as series of polypeptides with M(r) 75,000, 70,000, 50,000, and 49,000. These radioactive polypeptides were found primarily in the ER (Chrispeels et al., 1982, J Cell Biol., 93:5- 14). During a subsequent chase period, newly synthesized reserve proteins were initially present in the protein bodies in the above-named polypeptides. Between 1 and 20 h later, radioactive legumin subunits (M(r) 40,000 and 19,000) and smaller vicilin polypeptides (M(r) 34,000, 30,000, 25,000, 18,000, 14,000, 13,000, and 12,000) appeared in the protein bodies. The appearance of these labeled polypeptides in the protein bodies was not the result of a slow transport from the ER (or cytoplasm). Newly synthesized legumin and vicilin polypeptides were assembled into oligomers of 8S and 7S, respectively, in the ER. They appeared in the protein bodies in these oligomeric forms before the appearance of the smaller polypeptides (M(r) less than 49,000). These results indicate that the smaller vicilin polypeptides (M(r) less than 49,000) arise delayed posttranslational processing of some or all of the larger vicilin polypeptides. The precursors of legumin are completely processed in the protein bodies 2-3 h after their synthesis. The processing of the vicilin precursors is much slower (6-20 h) and only a fraction of the precursor molecules are processed. As a result both large (M(r) more than 49,000) and small polypeptides of vicilin accumulate in the protein bodies, whereas legumin accumulates only as polypeptides of M(r) 40,000 and 19,000. 相似文献
138.
139.
140.
The chaetognaths, or arrowworms, constitute a small and enigmatic phylum of
marine invertebrates whose phylogenetic affinities have long been
uncertain. A popular hypothesis is that the chaetognaths are the sister
group of the major deuterostome phyla: chordates, hemichordates, and
echinoderms. Here we attempt to determine the affinities of the
chaetognaths by using molecular sequence data. We describe the isolation
and nucleotide sequence determination of 18S ribosomal DNA from one species
of chaetognath and one acanthocephalan. Extensive phylogenetic analyses
employing a suite of phylogenetic reconstruction methods (maximum
parsimony, maximum likelihood, evolutionary parsimony, and two distance
methods) suggest that the hypothesized relationship between chaetognaths
and the deuterostomes is incorrect. In contrast, we propose that the
lineage leading to the chaetognaths arose prior to the advent of the
coelomate metazoa.
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