全文获取类型
收费全文 | 272篇 |
免费 | 16篇 |
国内免费 | 1篇 |
专业分类
289篇 |
出版年
2021年 | 5篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 11篇 |
2014年 | 11篇 |
2013年 | 15篇 |
2012年 | 17篇 |
2011年 | 8篇 |
2010年 | 13篇 |
2009年 | 9篇 |
2008年 | 12篇 |
2007年 | 11篇 |
2006年 | 6篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 4篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 10篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1977年 | 2篇 |
1976年 | 6篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 4篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1967年 | 3篇 |
1933年 | 1篇 |
1924年 | 1篇 |
1923年 | 1篇 |
排序方式: 共有289条查询结果,搜索用时 15 毫秒
31.
Background
Two-dimensional data colourings are an effective medium by which to represent three-dimensional data in two dimensions. Such "color-grid" representations have found increasing use in the biological sciences (e.g. microarray 'heat maps' and bioactivity data) as they are particularly suited to complex data sets and offer an alternative to the graphical representations included in traditional statistical software packages. The effectiveness of color-grids lies in their graphical design, which introduces a standard for customizable data representation. Currently, software applications capable of generating limited color-grid representations can be found only in advanced statistical packages or custom programs (e.g. micro-array analysis tools), often associated with steep learning curves and requiring expert knowledge. 相似文献32.
Gerson Dierley Keppeke Eunice Nunes Maria Lucia Gomes Ferraz Eduardo Ant?nio Benedito Silva Celso Granato Edward K. L. Chan Luís Eduardo C. Andrade 《PloS one》2012,7(9)
Background
A novel pattern in the indirect immunofluorescence antinuclear antibody assay on HEp-2 cells (IIF-HEp-2) characterized by cytoplasmic rods and rings (RR) was reported in HCV patients, but stringent disease specificity studies and longitudinal analysis are lacking. We investigated the clinical significance of anti-RR in an HCV cohort with up to a 12-month treatment follow up.Methodology/Results
597 patients (342 HCV, 55 HCV/HIV, 200 non-HCV) were screened and titered for anti-RR. Serial samples were available from 78 of 176 treated and 27 of 166 untreated patients. Anti-RR was detected in 14.1% of 342 HCV patients, 9.1% of 55 HCV/HIV, 3.4% of 29 Hepatitis B, and none of 171 non-HCV (p<0.0001; HCV versus non-HCV). Anti-RR was present in 38% of 108 patients receiving interferon-α/ribavirin, but none in 26 receiving either interferon-α or ribavirin, or 166 untreated patients (p<0.0001). Other IIF-HEp-2 patterns were more frequently associated with interferon-α treatment alone (52.2%) as compared to interferon-α/ribavirin (25%), ribavirin alone (33.3%), and no therapy (26.5%). Anti-RR frequency was not associated with sex, age, ethnicity, HCV genotype or viral load. Anti-RR occurred only after initiation of treatment, beginning as early as 1 month (6%), but by the sixth month >47% tested positive for anti-RR. The anti-RR titer generally increased with sustained treatment and remained high in 53% of patients. After treatment, anti-RR titer was negative in 41%. Non-responders to HCV therapy were 77% in anti-RR-positive versus 64% in anti-RR-negative patients. Response to treatment was not associated with anti-RR titer or the dynamics of anti-RR reactivity during and after treatment.Conclusions
The exquisite association of anti-RR reactivity with combined interferon-α/ribavirin therapy in HCV patients represents a unique model for drug-induced autoantibody generation in humans as demonstrated by the fact that a significant fraction of patients who have anti-RR during therapy becomes anti-RR-negative after completion of therapy. 相似文献33.
34.
Joint Report of the First International Comparison Test on Swine Lymphocyte Alloantigens (SLA) 总被引:5,自引:0,他引:5
CH. RENARD B. KRISTENSEN C. GAUTSCHI V. HRUBAN M. FREDHOLM M. VAIMAN 《Animal genetics》1988,19(1):63-72
The first international comparison test on swine lymphocyte alloantigens (SLA) was held in Helsinki, Finland in July 1986. The results reported were based on a comparison of 157 alloantisera originating from six laboratories. The antisera were tested against a selected panel of 264 lymphocyte samples belonging to four laboratories. The most common breeds in Europe were chosen for this first comparison test (Landrace and Large White). Eighteen of the 31 previously known specificities were confirmed and a new nomenclature was established. 相似文献
35.
36.
37.
L Granato A Brandes C Bruni A V Greco G Mingrone 《Journal of applied physiology》2004,96(3):1045-1054
A respiratory chamber is used for monitoring O(2) consumption (Vo(2)), CO(2) production (Vco(2)), and respiratory quotient (RQ) in humans, enabling long term (24-h) observation under free-living conditions. Computation of Vo(2) and Vco(2) is currently done by inversion of a mass balance equation, with no consideration of measurement errors and other uncertainties. To improve the accuracy of the results, a new mathematical model is suggested in the present study explicitly accounting for the presence of such uncertainties and error sources and enabling the use of optimal filtering methods. Experiments have been realized, injecting known gas quantities and estimating them using the proposed mathematical model and the Kalman-Bucy (KB) estimation method. The estimates obtained reproduce the known production rates much better than standard methods; in particular, the mean error when fitting the known production rates is 15.6 +/- 0.9 vs. 186 +/- 36 ml/min obtained using a conventional method. Experiments with 11 humans were carried out as well, where Vo(2) and Vco(2) were estimated. The variance of the estimation errors, produced by the KB method, appears relatively small and rapidly convergent. Spectral analysis is performed to assess the residual noise content in the estimates, revealing large improvement: 2.9 +/- 0.8 vs. 3,440 +/- 824 (ml/min)(2) and 1.8 +/- 0.5 vs. 2,057 +/- 532 (ml/min)(2), respectively, for Vo(2) and Vco(2) estimates. Consequently, the accuracy of the computed RQ is also highly improved (0.3 x 10(-4) vs. 800 x 10(-4)). The presented study demonstrates the validity of the proposed model and the improvement in the results when using a KB estimation method to resolve it. 相似文献
38.
39.
Jenny Bulgarelli Laura Fiammenghi Serena Cassan Anna Maria Granato Massimiliano Petrini Elena Pancisi Valentina Soldati Francesco De Rosa Laura Ridolfi Angela Riccobon Massimo Guidoboni 《Cytotherapy》2018,20(6):851-860
Background
Dendritic cells (DCs) are the most efficient antigen-presenting cells and act at the center of the immune system owing to their ability to control both immune tolerance and immunity. In cancer immunotherapy, DCs play a key role in the regulation of the immune response against tumors and can be generated ex vivo with different cytokine cocktails. Methods. We evaluated the feasibility of dinoprostone (PGE2) replacement with the molecular analog sulprostone, in our good manufacturing practice (GMP) protocol for the generation of DC-based cancer vaccine. We characterized the phenotype and the function of DCs matured in the presence of sulprostone as a potential substitute of dinoprostone in the pro-inflammatory maturation cocktail consisting of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6. Results. We found that sulprostone invariably reduces the recovery, but does not significantly modify the viability and the purity of DCs. The presence of sulprostone in the maturation cocktail increases the adhesion of single cells and of clusters of DCs to the flask, making them more similar to their immature counterpart in terms of adhesion and spreading proprieties. Moreover, we observed that sulprostone impairs the expression of co-stimulatory molecules and the spontaneous as well as the directed migration capacity of DCs.Discussion
These findings underscore that the synthetic analog sulprostone strongly reduces the functional quality of DCs, thus cannot replace dinoprostone in the maturation cocktail of monocyte-derived DCs. 相似文献40.
Group I introns are proposed to have become mobile following the
acquisition of open reading frames (ORFs) that encode highly specific DNA
endonucleases. This proposal implies that intron ORFs could behave as
autonomously mobile entities. This was supported by abundant circumstantial
evidence but no experiment of ORF transfer from an ORF- containing intron
to its ORF-less counterpart has been described. In this paper we present
such experiments, which demonstrate the efficient mobility of the
mitochondrial nad1-i4-orf1 between two Podospora strains. The homing of
this mobile ORF was accompanied by a bidirectional co-conversion that did
not systematically involve the whole intron sequence. Orf1 acquisition
would be the most recent step in the evolution of the nad1-i4 intron, which
has resulted in many strains of Podospora having an intron with two ORFs
(biorfic) and four splicing pathways. We show that two of the splicing
events that operate in this biorfic intron, as evidenced by PCR
experiments, are generated by a 5'-alternative splice site, which is most
probably a remnant of the monoorfic ancestral form of the intron. We
propose a sequential evolution model that is consistent with the four
organizations of the corresponding nad1 locus that we found among various
species of the Pyrenomycete family; these organizations consist of no
intron, an intron alone, a monoorfic intron, and a biorfic intron.
相似文献