全文获取类型
收费全文 | 111篇 |
免费 | 13篇 |
出版年
2023年 | 1篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 5篇 |
2013年 | 6篇 |
2012年 | 10篇 |
2011年 | 8篇 |
2010年 | 4篇 |
2009年 | 7篇 |
2008年 | 10篇 |
2007年 | 7篇 |
2006年 | 7篇 |
2005年 | 6篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1986年 | 1篇 |
1981年 | 2篇 |
1977年 | 3篇 |
1975年 | 2篇 |
排序方式: 共有124条查询结果,搜索用时 73 毫秒
91.
92.
93.
Nagesh Ragavendra JW Ju James W Sayre Sharon Hirschowitz Inder Chopra Michael W Yeh 《Journal of biological engineering》2008,2(1):1-4
Background
Human solid tumors that are hard or firm on physical palpation are likely to be cancerous, a clinical maxim that has been successfully applied to cancer screening programs, such as breast self-examination. However, the biological relevance or prognostic significance of tumor hardness remains poorly understood. Here we present a fracture mechanics based in vivo approach for characterizing the fracture toughness of biological tissue of human thyroid gland tumors.Methods
In a prospective study, 609 solid thyroid gland tumors were percutaneously probed using standard 25 gauge fine needles, their tissue toughness ranked on the basis of the nature and strength of the haptic force feedback cues, and subjected to standard fine needle biopsy. The tumors' toughness rankings and final cytological diagnoses were combined and analyzed. The interpreting cytopathologist was blinded to the tumors' toughness rankings.Results
Our data showed that cancerous and noncancerous tumors displayed remarkable haptically distinguishable differences in their material toughness.Conclusion
The qualitative method described here, though subject to some operator bias, identifies a previously unreported in vivo approach to classify fracture toughness of a solid tumor that can be correlated with malignancy, and paves the way for the development of a mechanical device that can accurately quantify the tissue toughness of a human tumor. 相似文献94.
Both avian and insect cuckoos must trick their hosts into accepting foreign eggs. In birds this is achieved through egg mimicry. Within the hornets the only known social parasite is the rare Vespa dybowskii. We investigated how the V. dybowskii queen induces tens or hundreds of host workers to accept her eggs and offspring. Since hydrocarbons function as recognition cues in social insects, we investigated these compounds from the surface of eggs and workers of V. dybowskii, both host species (V. simillima and V. crabro) and an additional four non-host species. We found that chemical mimicry of the hosts’ colony odour and their eggs normally associated with wasps was not being employed by V. dybowskii. Chemical insignificance is also unlikely as the amounts of hydrocarbons extracted from parasite, host and non-host eggs were similar. Eggs of V. dybowskii may survive in part due to being chemically transparent, as methyl-branched compounds only represent a tiny proportion (<1%) of the parasites hydrocarbon profile but a large proportion (26–41%) in both host species. However, the functions of various hydrocarbon groups need to be investigated in the hornets before this new acceptance mechanism of parasite eggs and adults is understood. 相似文献
95.
Molecular phylogeny of the major arthropod groups indicates polyphyly of crustaceans and a new hypothesis for the origin of hexapods 总被引:18,自引:6,他引:12
A phylogeny of the arthropods was inferred from analyses of amino acid
sequences derived from the nuclear genes encoding elongation factor-1 alpha
and the largest subunit of RNA polymerase II using maximum- parsimony,
neighbor-joining, and maximum-likelihood methods. Analyses of elongation
factor-1 alpha from 17 arthropods and 4 outgroup taxa recovered many
arthropod clades supported by previous morphological studies, including
Diplopoda, Myriapoda, Insecta, Hexapoda, Branchiopoda (Crustacea), Araneae,
Tetrapulmonata, Arachnida, Chelicerata, and Malacostraca (Crustacea).
However, counter to previous studies, elongation factor-1 alpha placed
Malacostraca as sister group to the other arthropods. Branchiopod
crustaceans were found to be more closely related to hexapods and myriapods
than to malacostracan crustaceans. Sequences for RNA polymerase II were
obtained from 11 arthropod taxa and were analyzed separately and in
combination with elongation factor-1 alpha. Results from these analyses
were concordant with those derived from elongation factor-1 alpha alone and
provided support for a Hexapoda/Branchiopoda clade, thus arguing against
the monophyly of the traditionally defined Atelocerata (Hexapoda +
Myriapoda).
相似文献
96.
Exposure of the outside of the isolated frog skin to a Ringer's solution, made hypertonic by the addition of mannitol, causes a rapid and sustained increase in transepithelial permeability through a structural distortion-a focal blistering-of the "tight" junctions of the outermost living cell layer. [(3)H]ouabain, used as an autoradiographic marker for the Na+-pump (Na+-K+-adenosine triphosphatase), is usually unable to penetrate the frog skin from the outside solution, but when added to a hypertonic mannitol- Ringer's solution in the outside bath it readily penetrates the epithelium, presumably through the opened shunt pathway. Radioautographic analysis of [(3)H]ouabain binding sites revealed that most of ouabain enters from the outside solution binds to the sites on the cell membranes of the stratum spinosum, as was the case when it was applied from the inside bath in an earlier study. The outer living cell layer, the first to be exposed to ouabain, does not appear to be the major site for the Na+-pump, and therefore, is not likely to be responsible for most of the active pumping of Na+. This result demonstrates that previous failure to show a high density of Na+-pump sites on the cells of the outermost layer, when [(3)H]ouabain was applied from the inside solution, was not due to the inability of the marker to reach these cells at a sufficient concentration to reveal all pump sites. These results provide further support for a model of Na+-transport across the frog skin which distributes the active pump step on the inward facing membranes of all living cells. 相似文献
97.
Yvonne van de Wal Yvonne M. C. Kooy Jan Woulter Drijfhout Reinout Amons Frits Koning 《Immunogenetics》1996,44(4):246-253
Genetic susceptibility to coeliac disease (CD) is strongly associated with the expression of theHLA-DQ2 (α1*0501, β1*0201) allele. There is evidence that this DQ2 molecule plays a role in the pathogenesis of CD as a restriction element for
gliadin-specific T cells in the gut. However, it remains largely unclear which fragments of gliadin can actually be presented
by the disease-associated DQ dimer. With a view to identifying possible CD-inducing antigens, we studied the peptide binding
properties of DQ2. For this purpose, peptides bound to HLA-DQ2 were isolated and characterized. Dominant peptides were found
to be derived from two self-proteins: in addition to several sizevariants of the invariant chain (li)-derived CLIP peptide,
a relatively large amount of an major histocompatibility complex (MHC) class I-derived peptide was found. Analogues of this
naturally processed epitope (MHClα46–63) were tested in a cell-free peptide binding competition assay to investigate the requirements
for binding to DQ2. First, a core sequence of 10 amino acids within the MHClα46–63 peptide was identified. By subsequent single
amino acid substitution analysis of this core sequence, five putative anchor residues were identified at relative positions
P1, P4, P6, P7, and P9. Replacement by the large, positively charged Lys at these positions resulted in a dramatic loss of
binding. However, several other non-conservative substitutions had little or no discernable effect on the binding capacity
of the peptides.
Substitutions at P1 and P4 were most critical, suggesting a more prominent role as anchor residues. Structural features of
the DQ2 molecule that may relate to the binding motif and to gluten sensitivity are discussed. 相似文献
98.
This report describes a lysozyme expressed at high levels in the stomach of
the hoatzin, the only known foregut-fermenting bird. Evolutionary
comparison places it among the calcium-binding lysozymes rather than among
the conventional types. Conventional lysozymes were recruited as digestive
enzymes twice in the evolution of mammalian foregut fermenters, and these
independently recruited lysozymes share convergent structural changes
attributed to selective pressures in the stomach. Biochemical convergence
and parallel amino acid replacements are observed in the hoatzin stomach
lysozyme even though it has a different genetic origin from the mammalian
examples and has undergone more than 300 million years of independent
evolution.
相似文献
99.
Khan S Bijker MS Weterings JJ Tanke HJ Adema GJ van Hall T Drijfhout JW Melief CJ Overkleeft HS van der Marel GA Filippov DV van der Burg SH Ossendorp F 《The Journal of biological chemistry》2007,282(29):21145-21159
Covalent conjugation of Toll-like receptor ligands (TLR-L) to synthetic antigenic peptides strongly improves antigen presentation in vitro and T lymphocyte priming in vivo. These molecularly well defined TLR-L-peptide conjugates, constitute an attractive vaccination modality, sharing the peptide antigen and a defined adjuvant in one single molecule. We have analyzed the intracellular trafficking and processing of two TLR-L conjugates in dendritic cells (DCs). Long synthetic peptides containing an ovalbumin cytotoxic T-cell epitope were chemically conjugated to two different TLR-Ls the TLR2 ligand, Pam(3)CysSK(4) (Pam) or the TLR9 ligand CpG. Rapid and enhanced uptake of both types of TLR-L-conjugated peptide occurred in DCs. Moreover, TLR-L conjugation greatly enhanced antigen presentation, a process that was dependent on endosomal acidification, proteasomal cleavage, and TAP translocation. The uptake of the CpG approximately conjugate was independent of endosomally-expressed TLR9 as reported previously. Unexpectedly, we found that Pam approximately conjugated peptides were likewise internalized independently of the expression of cell surface-expressed TLR2. Further characterization of the uptake mechanisms revealed that TLR2-L employed a different uptake route than TLR9-L. Inhibition of clathrin- or caveolin-dependent endocytosis greatly reduced uptake and antigen presentation of the Pam-conjugate. In contrast, internalization and antigen presentation of CpG approximately conjugates was independent of clathrin-coated pits but partly dependent on caveolae formation. Importantly, in contrast to the TLR-independent uptake of the conjugates, TLR expression and downstream TLR signaling was required for dendritic cell maturation and for priming of na?ve CD8(+) T-cells. Together, our data show that targeting to two distinct TLRs requires distinct uptake mechanism but follows similar trafficking and intracellular processing pathways leading to optimal antigen presentation and T-cell priming. 相似文献
100.
Zendman AJ Raijmakers R Nijenhuis S Vossenaar ER Tillaart Mv Chirivi RG Raats JM van Venrooij WJ Drijfhout JW Pruijn GJ 《Analytical biochemistry》2007,369(2):232-240
Members of the family of peptidylarginine deiminases (PADs, EC 3.5.3.15) catalyze the posttranslational modification of peptidylarginine into peptidylcitrulline. Citrulline-containing epitopes have been shown to be major and specific targets of autoantibodies produced by rheumatoid arthritis patients. Recently, the citrullination of histone proteins by PAD enzyme was reported to influence gene expression levels. These findings greatly increase the interest in the PAD enzymes and their activities. A few procedures to monitor PAD activity in biological samples have been described previously. However, these assays either have low sensitivity or are rather laborious. Here we describe a reliable and reproducible method for the determination of PAD activity in both purified and crude samples. The method is based on the quantification of PAD-dependent citrullination of peptides, immobilized in microtiter plates, using antibodies that are exclusively reactive with the reaction product(s). Our results demonstrate that this antibody-based assay for PAD activity, called ABAP, is very sensitive and can be applied to monitor PAD activity in biological samples. 相似文献