全文获取类型
收费全文 | 1606篇 |
免费 | 127篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 32篇 |
2020年 | 20篇 |
2019年 | 27篇 |
2018年 | 20篇 |
2017年 | 26篇 |
2016年 | 42篇 |
2015年 | 68篇 |
2014年 | 55篇 |
2013年 | 120篇 |
2012年 | 117篇 |
2011年 | 127篇 |
2010年 | 99篇 |
2009年 | 90篇 |
2008年 | 121篇 |
2007年 | 90篇 |
2006年 | 87篇 |
2005年 | 93篇 |
2004年 | 99篇 |
2003年 | 96篇 |
2002年 | 101篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 21篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 14篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 11篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1734条查询结果,搜索用时 15 毫秒
21.
Dominik Karch Keun-Sun Kim Katarzyna Wochner Heike Philippi Joachim Pietz Hartmut Dickhaus 《Journal of biomechanics》2010,43(9):1844-1848
In motion capture applications using electromagnetic tracking systems the process of anatomical calibration associates the technical frames of sensors attached to the skin with the human anatomy. Joint centers and axes are determined relative to these frames. A change of orientation of the sensor relative to the skin renders this calibration faulty. This sensitivity regarding sensor displacement can turn out to be a serious problem with movement recordings of several minutes duration. We propose the “dislocation distance” as a novel method to quantify sensor displacement and to detect gradual and sudden changes of sensor orientation. Furthermore a method to define a so called fixed technical frame is proposed as a robust reference frame which can adapt to a new sensor orientation on the skin. The proposed methods are applied to quantify the effects of sensor displacement of 120 upper and lower limb movement recordings of newborns revealing the need for a method to compensate for sensor displacement. The reliability of the fixed technical frame is quantified and it is shown that trend and dispersion of the dislocation distance can be significantly reduced. A working example illustrates the consequences of sensor displacement on derived angle time series and how they are avoided using the fixed technical frame. 相似文献
22.
23.
Purinergic Signalling - 相似文献
24.
We studied the variation of small-scale swimming behaviour in eight Bosmina cornuta and ten B. pellucida clones in response to key environmental factors to test whether swimming behaviour and genotypes are linked in non-Daphnia cladocerans. We quantified (1) the short-term responses to changes in temperature, light intensity and pH, (2) the response to long-term temperature acclimation, and (3) the pH-related survival rates. Vertical swimming activity S was quantified in cuvette experiments as crossings of a line at 2 cm height per individual an hour. S differed significantly among species and conspecific clones. At any temperature, light intensity and pH tested, B. cornuta (clone variation: 40-58 crossings/ind.- h) showed a higher vertical swimming activity than B. pellucida (clone variation: 25-48 crossings/ind.- h). A short-term change of water temperature (range tested: 10-25C) only affected S of B. cornuta, whereas that of B. pellucida remained unaltered. In contrast, S increased with rising temperature following long-term temperature acclimation (range tested: 10-20C) in both species. Swimming activity was inversely related to the light intensity (range tested: 60-60,000 lux), but decrease of activity was stronger in B. pellucida (44′ 12 crossings/ind - h) than in B. cornuta (50′ 40 crossings/ind.- h). Short-term changes of pH (range tested: 4-6) did not influence swimming activity in any species, although a prolonged exposure (24 h) to pH 4 was lethal. Thus, Bosmina showed behavioural responses which permit to distinguish between the species and which are related to their seasonal succession and distribution pattern. 相似文献
25.
Marion Haensler Heike Schuerer Ulrich Hahn Hans-Dieter Jakubke 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1267-1274
Abstract Synthesis of guanylyl(3′→5′)cytidine catalysed by RNase T1 variants (Tyr42Trp, Tyr24Trp and GluSSAla) was studied in frozen aqueous systems at-10°C and in solution at 0°C. Freezing the reaction mixture resulted in significantly enhanced dinucleoside monophosphate yields independently of the effect of mutation on substrate binding and catalytic mechanism. We assume that the protonation state of the catalytic residues is influenced by freezing, possibly due to conformational changes of the enzyme proteins. 相似文献
26.
27.
28.
Stefan Balabanov Thomas Wilhelm Simone Venz Gunhild Keller Christian Scharf Heike Pospisil Melanie Braig Christine Barett Carsten Bokemeyer Reinhard Walther Tim H. Brümmendorf Andreas Schuppert 《PloS one》2013,8(1)
In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs. 相似文献
29.
Joanne Van Der Velden Grace Sum Donna Barker Emmanuel Koumoundouros Garry Barcham Heike Wulff Neil Castle Peter Bradding Kenneth Snibson 《PloS one》2013,8(6)
Background
The Ca2+-activated K+ channel KCa3.1 is expressed in several structural and inflammatory airway cell types and is proposed to play an important role in the pathophysiology of asthma. The aim of the current study was to determine whether inhibition of KCa3.1 modifies experimental asthma in sheep.Methodology and Principal Findings
Atopic sheep were administered either 30 mg/kg Senicapoc (ICA-17073), a selective inhibitor of the KCa3.1-channel, or vehicle alone (0.5% methylcellulose) twice daily (orally). Both groups received fortnightly aerosol challenges with house dust mite allergen for fourteen weeks. A separate sheep group received no allergen challenges or drug treatment. In the vehicle-control group, twelve weeks of allergen challenges resulted in a 60±19% increase in resting airway resistance, and this was completely attenuated by treatment with Senicapoc (0.25±12%; n = 10, P = 0.0147). The vehicle-control group had a peak-early phase increase in lung resistance of 82±21%, and this was reduced by 58% with Senicapoc treatment (24±14%; n = 10, P = 0.0288). Senicapoc-treated sheep also demonstrated reduced airway hyperresponsiveness, requiring a significantly higher dose of carbachol to increase resistance by 100% compared to allergen-challenged vehicle-control sheep (20±5 vs. 52±18 breath-units of carbachol; n = 10, P = 0.0340). Senicapoc also significantly reduced eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and reduced vascular remodelling.Conclusions
These findings suggest that KCa3.1-activity contributes to allergen-induced airway responses, inflammation and vascular remodelling in a sheep model of asthma, and that inhibition of KCa3.1 may be an effective strategy for blocking allergen-induced airway inflammation and hyperresponsiveness in humans. 相似文献30.
Katy Morgan Roach Stephen Mark Duffy William Coward Carol Feghali-Bostwick Heike Wulff Peter Bradding 《PloS one》2013,8(12)