全文获取类型
收费全文 | 132篇 |
免费 | 14篇 |
出版年
2019年 | 2篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 8篇 |
2015年 | 11篇 |
2014年 | 13篇 |
2013年 | 6篇 |
2012年 | 7篇 |
2011年 | 5篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 1篇 |
2007年 | 2篇 |
2006年 | 3篇 |
2005年 | 7篇 |
2004年 | 2篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 7篇 |
1995年 | 2篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有146条查询结果,搜索用时 15 毫秒
91.
Nicole Willems Frances C Bach Saskia G M Plomp Mattie HP van Rijen Jeannette Wolfswinkel Guy CM Grinwis Clemens Bos Gustav J Strijkers Wouter JA Dhert Bj?rn P Meij Laura B Creemers Marianna A Tryfonidou 《Arthritis research & therapy》2015,17(1)
IntroductionStrategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain.MethodsCanine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue.ResultsIn vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7.ConclusionsAn intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0625-2) contains supplementary material, which is available to authorized users. 相似文献92.
93.
Pearson T Wattis JA O'Malley B Pickersgill L Blackburn H Jackson KG Byrne HM 《Journal of mathematical biology》2009,58(6):845-880
Elevated levels of low-density-lipoprotein cholesterol (LDL-C) in the plasma are a well-established risk factor for the development
of coronary heart disease. Plasma LDL-C levels are in part determined by the rate at which LDL particles are removed from
the bloodstream by hepatic uptake. The uptake of LDL by mammalian liver cells occurs mainly via receptor-mediated endocytosis, a process which entails the binding of these particles to specific receptors in specialised
areas of the cell surface, the subsequent internalization of the receptor–lipoprotein complex, and ultimately the degradation
and release of the ingested lipoproteins’ constituent parts. We formulate a mathematical model to study the binding and internalization
(endocytosis) of LDL and VLDL particles by hepatocytes in culture. The system of ordinary differential equations, which includes
a cholesterol-dependent pit production term representing feedback regulation of surface receptors in response to intracellular
cholesterol levels, is analysed using numerical simulations and steady-state analysis. Our numerical results show good agreement
with in vitro experimental data describing LDL uptake by cultured hepatocytes following delivery of a single bolus of lipoprotein.
Our model is adapted in order to reflect the in vivo situation, in which lipoproteins are continuously delivered to the hepatocyte.
In this case, our model suggests that the competition between the LDL and VLDL particles for binding to the pits on the cell
surface affects the intracellular cholesterol concentration. In particular, we predict that when there is continuous delivery
of low levels of lipoproteins to the cell surface, more VLDL than LDL occupies the pit, since VLDL are better competitors
for receptor binding. VLDL have a cholesterol content comparable to LDL particles; however, due to the larger size of VLDL,
one pit-bound VLDL particle blocks binding of several LDLs, and there is a resultant drop in the intracellular cholesterol
level. When there is continuous delivery of lipoprotein at high levels to the hepatocytes, VLDL particles still out-compete
LDL particles for receptor binding, and consequently more VLDL than LDL particles occupy the pit. Although the maximum intracellular
cholesterol level is similar for high and low levels of lipoprotein delivery, the maximum is reached more rapidly when the
lipoprotein delivery rates are high. The implications of these results for the design of in vitro experiments is discussed.
相似文献
94.
Kathryn E Wheatley Corey JA Bradshaw Robert G Harcourt Lloyd S Davis Mark A Hindell 《BMC veterinary research》2006,2(1):1-8
Background
Postweaning diarrhoea (PWD) in pigs is usually the main infectious problem of large-scale farms and is responsible for significant losses worldwide. The disease is caused mainly by enterotoxigenic E. coli (ETEC) and Shiga-toxin producing E. coli (STEC). In this study a total of 101 E. coli isolated from pigs with PWD in Slovakia were characterized using phenotypic and genotypic methods.Results
These 101 isolates belonged to 40 O:H serotypes. However, 57% of the isolates belonged to only six serotypes (O9:H51, O147:H-, O149:H10, O163:H-, ONT:H-, and ONT:H4), including two new serotypes (O163:H- and ONT:H4) not previously found among porcine ETEC and STEC isolated in other countries. Genes for EAST1, STb, STa, LT and Stx2e toxins were identified in 64%, 46%, 26%, 20%, and 5% of isolates, respectively. PCR showed that 35% of isolates carried genes for F18 colonization factor, and further analyzed by restriction endonuclease revealed that all of them were F18ac. Genes for F4 (K88), F6 (P987), F17, F5 (K99), F41, and intimin (eae gene) adhesins were detected in 19 %, 5%, 3%, 0.9%, 0.9%, and 0.9% of the isolates, respectively. The study of genetic diversity, carried out by PFGE of 46 representative ETEC and STEC isolates, revealed 36 distinct restriction profiles clustered in eight groups. Isolates of the same serotype were placed together in the dendrogram, but high degree of polymorphism among certain serotypes was detected.Conclusion
Seropathotype O149:H10 LT/STb/EAST1/F4 (14 isolates) was the most commonly detected followed by O163:H- EAST1/F18 (six isolates), and ONT:H4 STa/STb/Stx2e/F18 (five isolates). Interestingly, this study shows that two new serotypes (O163:H- and ONT:H4) have emerged as pig pathogens in Slovakia. Furthermore, our results show that there is a high genetic variation mainly among ETEC of O149:H10 serotype. 相似文献95.
Price DJ Campbell PG Sutton AG Grech ED Davies A Hall JA De Belder MA 《International journal of cardiovascular interventions》2001,4(1):15-20
BACKGROUND: The EPISTENT trial reported improved early outcomes with routine use of abciximab after coronary stenting. Increasing use of stents means that routine abciximab adds significantly to costs of percutaneous coronary intervention (PCI). This paper reports the results of a protocol encouraging restriction of abciximab therapy to high-risk patients only. METHODS: Data were collected prospectively over a 34-month period for patients undergoing PCI with stenting. In addition to those who fulfilled criteria for inclusion in the EPISTENT trial, patients treated in the setting of acute myocardial infarction (AMI) were studied. Demographic data, procedural details and early clinical outcomes were recorded. RESULTS: Of 808 patients studied, 601 fulfilled EPISTENT inclusion criteria and comprised 367 patients (45%) treated for stable angina and 234 (30%) treated for unstable or post-infarct angina. The additional 207 patients (25%) were treated during AMI. The 808 patients received a total of 981 stents. Abciximab was given in only 88 cases (10.9%). Major adverse clinical events occurred in 39 patients (4.8%). CONCLUSION: Selective use of abciximab for patients undergoing coronary stenting can be associated with outcomes equivalent to those reported for routine use, but with significant cost savings. 相似文献
96.
97.
98.
A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony 总被引:24,自引:1,他引:23
The method of evolutionary parsimony--or operator invariants--is a
technique of nucleic acid sequence analysis related to parsimony analysis
and explicitly designed for determining evolutionary relationships among
four distantly related taxa. The method is independent of substitution
rates because it is derived from consideration of the group properties of
substitution operators rather than from an analysis of the probabilities of
substitution in branches of a tree. In both parsimony and evolutionary
parsimony, three patterns of nucleotide substitution are associated
one-to-one with the three topologically linked trees for four taxa. In
evolutionary parsimony, the three quantities are operator invariants. These
invariants are the remnants of substitutions that have occurred in the
interior branch of the tree and are analogous to the substitutions assigned
to the central branch by parsimony. The two invariants associated with the
incorrect trees must equal zero (statistically), whereas only the correct
tree can have a nonzero invariant. The chi 2-test is used to ascertain the
nonzero invariant and the statistically favored tree. Examples, obtained
using data calculated with evolutionary rates and branchings designed to
camouflage the true tree, show that the method accurately predicts the
tree, even when substitution rates differ greatly in neighboring peripheral
branches (conditions under which parsimony will consistently fail). As the
number of substitutions in peripheral branches becomes fewer, the parsimony
and the evolutionary-parsimony solutions converge. The method is robust and
easy to use.
相似文献
99.
Alves-Gomes JA; Orti G; Haygood M; Heiligenberg W; Meyer A 《Molecular biology and evolution》1995,12(2):298-318
The order Gymnotiformes (South American electric fishes) is a fascinating
assemblage of freshwater fishes that share the unusual ability to produce
and sense electric fields used for electrolocation and social
communication. In the last few decades, the electrogenic and electrosensory
systems (EES) of these fish have served as an excellent model to study
motor and sensory physiology in vertebrates. In an attempt to the evolution
of characters associated with the EES in the group, we applied
maximum-parsimony (MP), minimum-evolution (ME), and maximum-likelihood (ML)
methods to analyze 302 aligned bases of the mitochondrial 12S rRNA and 416
bases of the mitochondrial 16S rRNA of 19 gymnotiform genera representing
all six recognized families. Six catfish genera (order Siluriformes) were
also sequenced and used as outgroups. The phylogenetic hypothesis resultant
from molecular data analysis differs in some respects from previous
hypotheses based on morphological studies. Our results were most
informative within the family level, as we were unable to elucidate the
relationships among deeper branches in this order with sufficient
confidence by using molecular data alone. The phylogenetic information of
both mitochondrial DNA segments appears to be affected by functional
constraints, and the resultant topologies were sensitive to different
weighting schemes and the algorithm used. Nonetheless, we found unanimous
support for the following phylogenetic relationships: (1) the family
Sternopygidae is an unnatural group, and Sternopygus is the sole
representative of a unique lineage within the order; (2) the family
Hypopomidae is not monophyletic; and (3) the order Gymnotiformes is
composed of at least six natural clades: Sternopygus, family Apteronotidae,
a new clade consisting of the remaining sternopygids, families Hypopomidae
+ Rhamphicthyidae, family Electrophoridae, and family Gymnotidae. By
combining molecular, morphological, and physiological information, we
propose a new hypothesis for the phylogeny of this group and suggest a new
family Eigenmanniidae n. (order Gymnotiformes).
相似文献
100.
Formation of enlarged mitochondria in a liver cell line in response to a synthetic glucocorticoid 下载免费PDF全文
JA Berliner 《The Journal of cell biology》1975,64(3):711-716
For a number of years it has been recognized that glucocorticoids cause alterations in liver cell morphology (6, 9). Several investigators have shown that in liver in vivo mitochondria can be enlarged to many times their normal volume by treatment with cortisone (13, 15). There is a concomitant decrease in mitochondrial number, and the results of Kimberg and Loeb suggest that this is due to mitochondrial fusion (7). However, the exact mechanism whereby mitochondrial volume is altered and whether in fact cortisone is the direct causal agent are not known due to the complexity of studying these questions in a whole animal system. We have found that dexamethasone sodium phosphate (dex), a synthetic glucocorticoid, causes the formation of enlarged mitochondria in a liver cell line RLC-GAI, which grows in defined medium. In this paper we present our observations on the amount of enlargement that occurs after 5 days of treatment. The formation of enlarged mitochondria is reversible upon removal of the hormone from the medium, and we have attempted to determine whether "mitochondrial" or "nonmitochondrial" inhibitors are more effective in blocking the return of mitochondria to their normal size when the hormone is removed. 相似文献