全文获取类型
收费全文 | 3846篇 |
免费 | 348篇 |
国内免费 | 3篇 |
专业分类
4197篇 |
出版年
2021年 | 40篇 |
2020年 | 33篇 |
2019年 | 53篇 |
2018年 | 56篇 |
2017年 | 43篇 |
2016年 | 75篇 |
2015年 | 113篇 |
2014年 | 172篇 |
2013年 | 180篇 |
2012年 | 227篇 |
2011年 | 218篇 |
2010年 | 174篇 |
2009年 | 153篇 |
2008年 | 225篇 |
2007年 | 237篇 |
2006年 | 216篇 |
2005年 | 231篇 |
2004年 | 198篇 |
2003年 | 177篇 |
2002年 | 201篇 |
2001年 | 71篇 |
2000年 | 51篇 |
1999年 | 53篇 |
1998年 | 58篇 |
1997年 | 37篇 |
1996年 | 38篇 |
1995年 | 45篇 |
1994年 | 32篇 |
1993年 | 37篇 |
1992年 | 34篇 |
1991年 | 34篇 |
1990年 | 44篇 |
1989年 | 34篇 |
1988年 | 36篇 |
1987年 | 36篇 |
1986年 | 19篇 |
1985年 | 38篇 |
1984年 | 28篇 |
1983年 | 26篇 |
1982年 | 31篇 |
1981年 | 29篇 |
1980年 | 31篇 |
1979年 | 19篇 |
1978年 | 19篇 |
1977年 | 22篇 |
1976年 | 26篇 |
1975年 | 28篇 |
1974年 | 35篇 |
1973年 | 19篇 |
1972年 | 23篇 |
排序方式: 共有4197条查询结果,搜索用时 15 毫秒
51.
52.
Floss DM Sack M Stadlmann J Rademacher T Scheller J Stöger E Fischer R Conrad U 《Plant biotechnology journal》2008,6(4):379-391
The stability and recovery of recombinant proteins expressed in plants are improved by fusion to elastin-like peptides (ELPs). In order to test the suitability of ELP for the production of pharmaceutical proteins, transgenic plants were created that individually expressed the light and heavy chains of the broadly neutralizing anti-human immunodeficiency virus type 1 (anti-HIV-1) monoclonal antibody 2F5, which is being evaluated as a microbicide component. The antibody chains were expressed both with and without a C-terminal ELP fusion. Crossing these plants in all combinations resulted in transgenic lines producing the full antibody in four formats, with ELP on either the light or heavy chains, on both or on neither. Characterization of the affinity-purified antibodies by surface plasmon resonance spectroscopy showed that the kinetic binding parameters were identical to those of a Chinese hamster ovary (CHO) cell counterpart lacking ELP. N -Glycan analysis showed that all four derivatives contained predominantly oligo-mannose-type N -glycans and that the ELP fusions had no significant effect on N -glycan structure. It was concluded that ELP fusion to the light chain, heavy chain or both chains of a plant-derived antibody had no adverse affects on protein quality, but had a positive impact on the yield. ELP fusions do not interfere with folding, assembly, trafficking in the secretory pathway or post-translational modification, but enhance stability whilst at the same time simplifying recovery. 相似文献
53.
Sahlmüller MC Strating JR Beck R Eckert P Popoff V Haag M Hellwig A Berger I Brügger B Wieland FT 《Traffic (Copenhagen, Denmark)》2011,12(6):682-692
COPI (coat protein I)-coated vesicles are implicated in various transport steps within the early secretory pathway. The major structural component of the COPI coat is the heptameric complex coatomer (CM). Recently, four isoforms of CM were discovered that may help explain various transport steps in which the complex has been reported to be involved. Biochemical studies of COPI vesicles currently use CM purified from animal tissue or cultured cells, a mixture of the isoforms, impeding functional and structural studies of individual complexes. Here we report the cloning into single baculoviruses of all CM subunits including their isoforms and their combination for expression of heptameric CM isoforms in insect cells. We show that all four isoforms of recombinant CM are fully functional in an in vitro COPI vesicle biogenesis assay. These novel tools enable functional and structural studies on CM isoforms and their subcomplexes and allow studying mutants of CM. 相似文献
54.
This review, comprised of our own data and that of others, provides a summary overview of histone deacetylase (HDAC) inhibition on intestinal inflammation as well as inflammation-mediated carcinogenesis. Experimental colitis in mice represents an excellent in vivo model to define the specific cell populations and target tissues modulated by inhibitors of HDAC. Oral administration of either suberyolanilide hydroxamic acid (SAHA) or ITF2357 results in an amelioration in these models, as indicated by a significantly reduced colitis disease score and histological score. This effect was paralleled by suppression of proinflammatory cytokines at the site of inflammation as well as specific changes in the composition of cells within the lamina propria. In addition, tumor number and size was significantly reduced in two models of inflammation-driven tumorigenesis, namely interleukin (IL)-10-deficient mice and the azoxymethane-dextran sulfate sodium (DSS) model, respectively. The mechanisms affected by HDAC inhibition, contributing to this antiinflammatory and antiproliferative potency will be discussed in detail. Furthermore, with regard to the relevance in human inflammatory bowel disease, the doses of ITF2357 considered safe in humans and the corresponding serum concentrations are consistent with the efficacious dosing used in our in vivo as well as in vitro experiments. Thus, the data strongly suggest that HDAC inhibitors could serve as a therapeutic option in inflammatory bowel disease. 相似文献
55.
56.
Rainer J. Klement Prasanta S. Bandyopadhyay Colin E. Champ Harald Walach 《Theoretical biology & medical modelling》2018,15(1):12
Background
Ketogenic therapy in the form of ketogenic diets or calorie restriction has been proposed as a metabolic treatment of high grade glioma (HGG) brain tumors based on mechanistic reasoning obtained mainly from animal experiments. Given the paucity of clinical studies of this relatively new approach, our goal is to extrapolate evidence from the greater number of animal studies and synthesize it with the available human data in order to estimate the expected effects of ketogenic therapy on survival in HGG patients. At the same time we are using this analysis as an example for demonstrating how Bayesianism can be applied in the spirit of a circular view of evidence.Results
A Bayesian hierarchical model was developed. Data from three human cohort studies and 17 animal experiments were included to estimate the effects of four ketogenic interventions (calorie restriction/ketogenic diets as monotherapy/combination therapy) on the restricted mean survival time ratio in humans using various assumptions for the relationships between humans, rats and mice. The impact of different biological assumptions about the relevance of animal data for humans as well as external information based on mechanistic reasoning or case studies was evaluated by specifying appropriate priors. We provide statistical and philosophical arguments for why our approach is an improvement over existing (frequentist) methods for evidence synthesis as it is able to utilize evidence from a variety of sources. Depending on the prior assumptions, a 30–70% restricted mean survival time prolongation in HGG patients was predicted by the models. The highest probability of a benefit (>?90%) for all four ketogenic interventions was obtained when adopting an enthusiastic prior based on previous case reports together with assuming synergism between ketogenic therapies with other forms of treatment. Combinations with other treatments were generally found more effective than ketogenic monotherapy.Conclusions
Combining evidence from both human and animal studies is statistically possible using a Bayesian approach. We found an overall survival-prolonging effect of ketogenic therapy in HGG patients. Our approach is best compatible with a circular instead of hierarchical view of evidence and easy to update once more data become available.57.
58.
Dr. Rainer Kollmann 《Planta》1960,54(6):611-640
Ohne ZusammenfassungMit 28 TextabbildungenTeilabdruck einer Dissertation der Math. naturw. Fakultät der Universität Bonn/D 5. Das vollständige Exemplar kann an der obigen Stelle eingesehen werden. Teil II folgt in Bd. 55, Heft 1 (1960). 相似文献
59.
Background
Anesthetic administration is increasingly guided by electroencephalography (EEG)-based monitoring, such as the bispectral index (BIS). However, during cardiopulmonary bypass (CPB), factors other than the administered hypnotic agents may influence EEG signals, and their effects on BIS values are unknown.Methods
This report is a secondary analysis of data from a prospective, controlled interventional study comparing the effect of sevoflurane administration guided by BIS monitoring (group SevoBIS) and constant administration of sevoflurane (group Sevo1.8Vol%) during CPB. Sevoflurane plasma concentration (SPC) was measured using gas chromatography. The relationships of BIS to SPC, CPB pump flow, arterial pressure, hematocrit, temperature, time on CPB, and patient characteristics were analysed.Results
No association was observed between BIS values and SPC in group SevoBIS. In group Sevo1.8Vol%, a 40 μg ml-1 increase in SPC, which encompassed the entire range of observed values of the SPC in this analysis, was associated with a decrease of 3.6 (95% confidence interval (CI): 1.1–6.1) in BIS values (p = 0.005). Each increase in CPB time of 10 minutes was associated with an increase in BIS values of 0.25 (95%CI: 0.11–0.39, p<0.001). Path analysis revealed that the BIS values of SevoBIS patients were 5.3 (95%CI: 3.2–7.5) units higher than those of Sevo1.8Vol% patients (p<0.001), which was the strongest effect on BIS values. Path analysis revealed a slope of 0.5 (95%CI: 0.3–0.7) BIS units per 1°C body temperature (p<0.001).Conclusion
BIS monitoring is insensitive to clinically relevant changes in SPC in individual patients during CPB. 相似文献60.