全文获取类型
收费全文 | 709篇 |
免费 | 50篇 |
出版年
2023年 | 3篇 |
2022年 | 13篇 |
2021年 | 20篇 |
2020年 | 14篇 |
2019年 | 11篇 |
2018年 | 17篇 |
2017年 | 7篇 |
2016年 | 14篇 |
2015年 | 42篇 |
2014年 | 22篇 |
2013年 | 28篇 |
2012年 | 58篇 |
2011年 | 45篇 |
2010年 | 18篇 |
2009年 | 28篇 |
2008年 | 34篇 |
2007年 | 38篇 |
2006年 | 33篇 |
2005年 | 42篇 |
2004年 | 40篇 |
2003年 | 21篇 |
2002年 | 15篇 |
2001年 | 17篇 |
2000年 | 12篇 |
1999年 | 11篇 |
1998年 | 18篇 |
1997年 | 7篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1992年 | 11篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1984年 | 4篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 7篇 |
1979年 | 8篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1968年 | 3篇 |
1967年 | 2篇 |
1966年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有759条查询结果,搜索用时 15 毫秒
1.
K.L. Chew S. Octavia R. Jureen R.T.P. Lin J.W.P. Teo 《Letters in applied microbiology》2021,73(3):286-293
The objective of the study was to evaluate the use of targeted multiplex Nanopore MinION amplicon re-sequencing of key Candida spp. from blood culture bottles to identify azole and echinocandin resistance associated SNPs. Targeted PCR amplification of azole (ERG11 and ERG3) and echinocandin (FKS) resistance-associated loci was performed on positive blood culture media. Sequencing was performed using MinION nanopore device with R9.4.1 Flow Cells. Twenty-eight spiked blood cultures (ATCC strains and clinical isolates) and 12 prospectively collected positive blood cultures with candidaemia were included. Isolate species included Candida albicans, Candida glabrata, Candida krusei, Candida parapsilosis, Candida tropicalis and Candida auris. SNPs that were identified on ERG and FKS genes using Snippy tool and CLC Genomic Workbench were correlated with phenotypic testing by broth microdilution (YeastOne™ Sensititre). Illumina whole-genome-sequencing and Sanger-sequencing were also performed as confirmatory testing of the mutations identified from nanopore sequencing data. There was a perfect agreement of the resistance-associated mutations detected by MinION-nanopore-sequencing compared to phenotypic testing for acquired resistance (16 with azole resistance; 3 with echinocandin resistance), and perfect concordance of the nanopore sequence mutations to Illumina and Sanger data. Mutations with no known association with phenotypic drug resistance and novel mutations were also detected. 相似文献
2.
E C Chew 《Acta anatomica》1980,108(2):156-159
Tannic acid was found to fix and stain glycocalyx heavily. After removal of the major component of surface glycopeptides by trypsin, the surface coat was stained vaguely, and after the treatment with collagenase, the surface coat was moderately stained. It is concluded that tannic acid stained non-specific surface glycopeptides. 相似文献
3.
Yi Ting Zhou Li Li Chew Sheng-cai Lin Boon Chuan Low 《Molecular biology of the cell》2010,21(18):3232-3246
The BNIP-2 and Cdc42GAP homology (BCH) domain is a novel regulator for Rho GTPases, but its impact on p50-Rho GTPase-activating protein (p50RhoGAP or Cdc42GAP) in cells remains elusive. Here we show that deletion of the BCH domain from p50RhoGAP enhanced its GAP activity and caused drastic cell rounding. Introducing constitutively active RhoA or inactivating GAP domain blocked such effect, whereas replacing the BCH domain with endosome-targeting SNX3 excluded requirement of endosomal localization in regulating the GAP activity. Substitution with homologous BCH domain from Schizosaccharomyces pombe, which does not bind mammalian RhoA, also led to complete loss of suppression. Interestingly, the p50RhoGAP BCH domain only targeted RhoA, but not Cdc42 or Rac1, and it was unable to distinguish between GDP and the GTP-bound form of RhoA. Further mutagenesis revealed a RhoA-binding motif (residues 85-120), which when deleted, significantly reduced BCH inhibition on GAP-mediated cell rounding, whereas its full suppression also required an intramolecular interaction motif (residues 169-197). Therefore, BCH domain serves as a local modulator in cis to sequester RhoA from inactivation by the adjacent GAP domain, adding to a new paradigm for regulating p50RhoGAP signaling. 相似文献
4.
D A Keire P Anton K F Faull E Ruth J H Walsh P Chew D Quisimoro M Territo J R Reeve 《The Journal of biological chemistry》2001,276(52):48847-48853
The structure of a small-molecule, non-peptide chemotactic factor has been determined from activity purified to apparent homogeneity from Helicobacter pylori supernatants. H. pylori was grown in brucella broth media until one liter of solution had 0.9 absorbance units. The culture was centrifuged, and the bacteria re-suspended in physiological saline and incubated at 37 degrees C for 4 h. A monocyte migration bioassay revealed the presence of a single active chemotactic factor in the supernatant from this incubation. The chemotactic factor was concentrated by solid phase chromatography and purified by reverse phase high pressure liquid chromatography. The factor was shown to be indistinguishable from diethyl phthalate (DEP) on the basis of multiple criteria including nuclear magnetic resonance spectroscopy, electron impact mass spectroscopy, UV visible absorption spectrometry, GC and high pressure liquid chromatography retention times, and chemotactic activity toward monocytes. Control experiments with incubated culture media without detectable bacteria did not yield detectable DEP, suggesting it is bacterially derived. It is not known if the bacteria produce diethyl phthalate de novo or if it is a metabolic product of a precursor molecule present in culture media. DEP produced by H. pylori in addition to DEP present in man-made products may contribute to the high levels of DEP metabolites observed in human urine. DEP represents a new class of chemotactic factor. 相似文献
5.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
相似文献
6.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
7.
8.
Cis-unsaturated free fatty acids (FFA) at concentrations between 10 and 30 microM suppressed the superoxide respiratory burst induced in human neutrophils by the chemotactic peptide, N-formylmethionyl-leucyl-phenylalanine (FMLP). Corresponding trans-isomers had a reduced efficacy while saturated FFA were inert. The effects of unsaturated FFA were maximally achieved after several min of preincubation with cells and reversed upon washing. Increased concentrations of Ca2+ in the medium also relieved the inhibition. Unsaturated FFA were equally effective in dampening the respiratory burst induced by fluoride ions but less so with bursts elicited by 9 nM phorbol myristate acetate (PMA). Moreover reactions triggered by higher concentrations (e.g., 100 nM) of PMA were resistant to the effects of FFA. Radioimmunoassays showed that unsaturated FFA directly elevated intracellular cyclic adenosine monophosphate (cAMP) by severalfold above basal levels. It is suggested that inhibition is brought about by unsaturated FFA perturbation of the neutrophil membrane structure, perhaps with an independent contribution from a cAMP-dependent mechanism. 相似文献
9.
Estrone sulfate was measured in the plasma of pregnant and nonpregnant gilts between Days 10 and 32 after estrus. Estrone sulfate was found to rise sharply in pregnant gilts beginning at Day 18 and to decline at Day 30 to Day 32. Estrone levels were not related to litter size. The level of estrone sulfate on Days 20, 22, 24 and 26 was significantly correlated with litter size at slaughter on Day 32. Reduction of the number of live fetuses by crushing them in utero at Day 40 or between Days 30 to 60 did not cause a subsequent reduction in the level of estrone sulfate, whereas reduction at Day 24 did cause a decline in estrone sulfate. The level of estrone sulfate in plasma of gilts at 20 to 28 days after mating was higher in pregnant than in nonpregnant gilts. The relative level of estrone sulfate would enable one to estimate litter size at Days 20 to 28 days but not later. Because of the limitations of the assay in exact quantitation of the levels of estrone sulfate, the results can only be considered qualitative. 相似文献
10.
A 40-year-old carpenter presented with vomiting due to duodenal obstruction. On further investigation he had partial obstruction of both ureters and occlusion of the inferior vena cava. At laparotomy a large retroperitoneal mass of fibrous tissue was found, which extended into the root of the mesentery of the small intestine and partially occluded the duodenum. There was enlargement of lymphatics and stasis of lymph throughout the mesentery. Hypoalbuminemia was present. 131I-labelled human serum albumin disappeared rapidly from the plasma and there was excessive loss of plasma albumin into the gastrointestinal tract, presumably owing to obstruction of the lymphatic drainage of the small intestine. Prompt improvement followed treatment with prednisolone. Steroids are apparently useful in this condition, early in the disease before irreversible fibrosis has developed. The presenting feature, vomiting due to duodenal obstruction, has been reported in retroperitoneal fibrosis only once before. This is the first report of protein-losing enteropathy in this disorder. 相似文献