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81.
A novel method, single-molecule anisotropy imaging, has been employed to simultaneously study lateral and rotational diffusion of fluorescence-labeled lipids on supported phospholipid membranes. In a fluid membrane composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, in which the rotational diffusion time is on the order of the excited-state lifetime of the fluorophore rhodamine, a rotational diffusion constant, D(rot) = 7 x 10(7) rad(2)/s, was determined. The lateral diffusion constant, measured by direct analysis of single-molecule trajectories, was D(lat) = 3.5 x 10(-8) cm(2)/s. As predicted from the free-volume model for diffusion, the results exhibit a significantly enhanced mobility on the nanosecond time scale. For membranes of DPPC lipids in the L(beta) gel phase, the slow rotational mobility permitted the direct observation of the rotation of individual molecules characterized by D(rot) = 1.2 rad(2)/s. The latter data were evaluated by a mean square angular displacement analysis. The technique developed here should prove itself profitable for imaging of conformational motions of individual proteins on the time scale of milliseconds to seconds. 相似文献
82.
H J Brandwein J A Lewicki S A Waldman F Murad 《The Journal of biological chemistry》1982,257(3):1309-1311
In our studies with purified soluble guanylate cyclase from rat lung, we have tested a number of guanosine 5'-triphosphate (GTP) analogues as substrates and inhibitors, 5'-Guanylylimidodiphosphate (GMP-P(NH)P), guanylyl (beta, gamma-methylene) diphosphate (GMP-P(CH2)P), and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) were found to be substrates for guanylate cyclase. GTP gamma S supported cyclic GMP formation at 20 or 75% of the rate seen with Mn2+-GTP and Mg2+-GTP, respectively. GMP-P(NH)P and GMP P(CH2)P supported cyclic GMP formation at 10-20% of the GTP rate with either cation cofactor. These analogues were found to have multiple Km values; one Km value was similar to GTP (150 microM with Mg2+, 20-70 microM with Mn2+), but an additional high affinity catalytic site (3 microM) was also observed. Guanosine tetraphosphate (Ki = 10 microM), adenosine triphosphate (Ki = 9 microM) and the 2'3'-dialdehyde derivative of GTP (dial GTP) (Ki = 1 microM) were not good substrates for the enzyme; however, they were potent competitive inhibitors. These GTP analogues will be useful tools for the study of GTP binding sites on guanylate cyclase and they may also help elucidate the effects of free radicals and other agents on guanylate cyclase regulation. 相似文献
83.
Background
Haplotype reconstruction is important in linkage mapping and association mapping of quantitative trait loci (QTL). One widely used statistical approach for haplotype reconstruction is simulated annealing (SA), implemented in SimWalk2. However, the algorithm needs a very large number of sequential iterations, and it does not clearly show if convergence of the likelihood is obtained. 相似文献84.
Thirty-three dairy farms in the Norwegian counties of ?stfold and Akershus in which cubicle sheds had been in use for at least
one year and with a herd size of less than 60 cows, were contacted and asked to participate in a study. The study focused
on heifers' use of cubicles and concentrate dispenser just after being transferred from rearing accommodation to the milking
herd. For each heifer, the farmer recorded cubicle use once nightly between 9 and 11 pm. The daily amount of concentrate released
in the dispenser and the allotted daily ration were also recorded. The recording period was 15 consecutive days for cubicle
use and 7 days for concentrate dispenser use. Cubicle refusal behaviour, i.e. lying outside the cubicles, was analysed by
logistic regression using rearing accommodation of heifers, herd size, heifer age, and housing layout as independent variables,
and herd as a clustering variable. On Day 2 after transfer, 34% of the heifers were showing cubicle refusal behaviour (N =
340). By Day 15 this percentage had dropped to 23. Cubicle refusal was lower throughout the whole period among heifers which
used the cubicles on the 3 first days after transfer compared to those which did not. This tendency could also be detected
several months later. The analysis showed cubicle refusal to be significantly associated with rearing accommodation (OR =
6.1, c.i.95%OR = 1.5–24.3, P = 0.01) and cubicle layout in the shed (OR = 0.2, c.i.95%OR = 0.0–0.7, P = 0.01). None of the tested variables were found to be significant for failure to use the concentrate dispenser,
a behaviour which was less frequent than cubicle refusal. However, 8 percent of the heifers did not visit the dispenser at
all throughout the 7 days of observation. 相似文献
85.
This study aims to obtain osmosis-induced swelling strains of normal and proteoglycan (PG) depleted articular cartilage using an ultrasound system and to investigate the changes in its mechanical properties due to the PG depletion using a layered triphasic model. The swelling strains of 20 cylindrical cartilage-bone samples collected from different bovine patellae were induced by decreasing the concentration of bath saline and monitored by the ultrasound system. The samples were subsequently digested by a trypsin solution for approximately 20 min to deplete proteoglycans, and the swelling behaviors of the digested samples were measured again. The bi-layered triphasic model proposed in our previous study (Wang et al., J Biomech Eng-Trans ASME 2007; 129: 413-422) was used to predict the layered aggregate modulus Hafrom the data of depth-dependent swelling strain, fixed charge density and water content. It was found that the region near the bone, for the normal specimens, had a significantly higher aggregate modulus (Ha1= 20.6±18.2 MPa) in comparison with the middle zone and the surface layer (Ha2= 7.8±14.5 MPa and Ha3= 3.6±3.2 MPa, respectively) (p < 0.001). The normalized thickness of the deep layer h1 was 0.68±0.20. After the trypsin digestion, the parametric values decreased to Ha1 = 13.6±9.6 MPa, Ha2 = 6.7±11.5 MPa, Ha3 = 2.7±3.2 MPa, and h1 = 0.57±0.28. Other models were also used to analyze data and the results were compared. This study showed that high-frequency ultrasound measurement combined with the triphasic modeling was capable of nondestructively quantifying the alterations in the layered mechanical properties of the proteoglycan-depleted articular cartilage. 相似文献
86.
Bart?PieterseEmail author Elisabeth?J?Quirijns Frank?HJ?Schuren Mari?t?J?van der Werf 《BMC bioinformatics》2005,6(1):238
Background
Clone-based microarrays, on which each spot represents a random genomic fragment, are a good alternative to open reading frame-based microarrays, especially for microorganisms for which the complete genome sequence is not available. Since the generation of a genomic DNA library is a random process, it is beforehand uncertain which genes are represented. Nevertheless, the genome coverage of such an array, which depends on different variables like the insert size and the number of clones in the library, can be predicted by mathematical approaches. When applying the classical formulas that determine the probability that a certain sequence is represented in a DNA library at the nucleotide level, massive amounts of clones would be necessary to obtain a proper coverage of the genome. 相似文献87.
Michiel?M?Zandbelt Judith?Vogelzangs Leo?BA?van de Putte Walther?J?van Venrooij Frank?HJ?van den HoogenEmail author 《Arthritis research & therapy》2003,6(1):R33
The presence of anti-α-fodrin autoantibodies has been reported to be a highly specific and sensitive test for the diagnosis of Sjögren's syndrome (SjS). We looked (in Nijmegen) for anti-α-fodrin, anti-Ro60, and anti-La autoantibodies in a cohort of 51 patients with rheumatic diseases (primary SjS [21], secondary SjS [6], rheumatoid arthritis [RA] [12], systemic lupus erythematosus [SLE] [6], and scleroderma [6]) and in 28 healthy subjects, using ELISA, immunoblotting, and immunoprecipitation. The same samples were analyzed with an alternative anti-α-fodrin ELISA in Hanover. The Nijmegen ELISA of the sera from primary SjS showed sensitivities of 43% and 48% for IgA- and IgG-type anti-α-fodrin antibodies, respectively. The Hanover ELISA showed sensitivities of 38% and 10% for IgA- and IgG-type anti-α-fodrin antibodies, respectively. The ELISAs for α-fodrin showed six (Nijmegen) and four (Hanover) anti-α-fodrin-positive RA sera. IgA and IgG anti-fodrin antibodies were also present in four patients with secondary SjS. The sensitivities of Ro60 and La-antibodies in the Nijmegen ELISA were 67% and 62%, respectively. Unlike anti-α-fodrin antibodies, all anti-Ro60 and anti-La positive sera could be confirmed by immunoblotting or RNA immunoprecipitation. Thus, anti-Ro and anti-La autoantibodies were more sensitive than anti-α-fodrin autoantibodies in ELISA and were more frequently confirmed by other techniques. Anti-La antibodies appear to be more disease-specific than anti-α-fodrin antibodies, which are also found in RA sera. Therefore, the measurement of anti-α-fodrin autoantibodies does not add much to the diagnosis of Sjögren's syndrome. 相似文献
88.
Klaffke HS Majerus P Märtlbauer E Stan HJ Tiebach R Usleber E Weber R 《Mycotoxin Research》2000,16(1):79
Accelerated solvent extraction (ASE) is an alternative sample extraction procedure for fumonisins in corn and corn products. ASE gave results comparable to that of a draft CEN method, but required less extraction time. Furthermore, ASE gave significantly higher quantitative values than another method reported for extraction of fumonisins (Trucksess et al., 1995). 相似文献
89.
Sean?HJ?Kim Andre?J?Jackson Rim?Hur C?Anthony?HuntEmail author 《Theoretical biology & medical modelling》2012,9(1):39
Objective
Develop and validate particular, concrete, and abstract yet plausible in silico mechanistic explanations for large intra- and interindividual variability observed for eleven bioequivalence study participants. Do so in the face of considerable uncertainty about mechanisms.Methods
We constructed an object-oriented, discrete event model called subject (we use small caps to distinguish computational objects from their biological counterparts). It maps abstractly to a dissolution test system and study subject to whom product was administered orally. A subject comprises four interconnected grid spaces and event mechanisms that map to different physiological features and processes. Drugs move within and between spaces. We followed an established, Iterative Refinement Protocol. Individualized mechanisms were made sufficiently complicated to achieve prespecified Similarity Criteria, but no more so. Within subjects, the dissolution space is linked to both a product-subject Interaction Space and the GI tract. The GI tract and Interaction Space connect to plasma, from which drug is eliminated.Results
We discovered parameterizations that enabled the eleven subject simulation results to achieve the most stringent Similarity Criteria. Simulated profiles closely resembled those with normal, odd, and double peaks. We observed important subject-by-formulation interactions within subjects.Conclusion
We hypothesize that there were interactions within bioequivalence study participants corresponding to the subject-by-formulation interactions within subjects. Further progress requires methods to transition currently abstract subject mechanisms iteratively and parsimoniously to be more physiologically realistic. As that objective is achieved, the approach presented is expected to become beneficial to drug development (e.g., controlled release) and to a reduction in the number of subjects needed per study plus faster regulatory review.90.
Martin HJ Busch Wolfgang Vollmann Dietrich HW Grönemeyer 《Biomedical engineering online》2006,5(1):35-20