全文获取类型
收费全文 | 4522篇 |
免费 | 323篇 |
国内免费 | 1篇 |
出版年
2023年 | 29篇 |
2022年 | 74篇 |
2021年 | 127篇 |
2020年 | 52篇 |
2019年 | 83篇 |
2018年 | 114篇 |
2017年 | 133篇 |
2016年 | 174篇 |
2015年 | 230篇 |
2014年 | 276篇 |
2013年 | 333篇 |
2012年 | 417篇 |
2011年 | 427篇 |
2010年 | 230篇 |
2009年 | 170篇 |
2008年 | 249篇 |
2007年 | 272篇 |
2006年 | 254篇 |
2005年 | 267篇 |
2004年 | 226篇 |
2003年 | 192篇 |
2002年 | 172篇 |
2001年 | 52篇 |
2000年 | 19篇 |
1999年 | 28篇 |
1998年 | 44篇 |
1997年 | 19篇 |
1996年 | 17篇 |
1995年 | 21篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 6篇 |
1988年 | 10篇 |
1987年 | 14篇 |
1985年 | 5篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1977年 | 5篇 |
1976年 | 6篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1967年 | 2篇 |
排序方式: 共有4846条查询结果,搜索用时 31 毫秒
951.
Joanna Kalucka Rindert Missiaen Maria Georgiadou Sandra Schoors Christian Lange Katrien De Bock Mieke Dewerchin Peter Carmeliet 《Cell cycle (Georgetown, Tex.)》2015,14(21):3379-3388
Cell division is a metabolically demanding process, requiring the production of large amounts of energy and biomass. Not surprisingly therefore, a cell''s decision to initiate division is co-determined by its metabolic status and the availability of nutrients. Emerging evidence reveals that metabolism is not only undergoing substantial changes during the cell cycle, but it is becoming equally clear that metabolism regulates cell cycle progression. Here, we overview the emerging role of those metabolic pathways that have been best characterized to change during or influence cell cycle progression. We then studied how Notch signaling, a key angiogenic pathway that inhibits endothelial cell (EC) proliferation, controls EC metabolism (glycolysis) during the cell cycle. 相似文献
952.
Katarzyna Szyba Maria Cieślak Golonka Kazimierz Gasiorowski Joanna Urban 《Biometals》1992,5(3):157-161
Copper(II) chromate and dichromate complexes with 2,2'-bipyridyl and 1,10-phenathroline were tested for their mutagenic activity in the standard Ames test. All of six tested complexes exhibited markedly lower mutagenic activity than the reference compounds--potassium dichromate and sodium chromate. The blockage of Cr(VI) reduction capability in the presence of the complex Cu2+ ion and the competition between copper and chromium ions in the interaction with cellular components are discussed in the light of the results of our previous chemical study. 相似文献
953.
We present a rapid method to isolate and analyze bacteriophage DNA. Cells are infected and phage replication is allowed to proceed normally for 30 to 60 min. Prior to DNA packaging and cell bursts, the infected cells (1 ml) are harvested and lysed by using a combination of lysozyme and sodium dodecyl sulfate treatments. The total DNA recovered is enriched for phage genomes, and restriction fragments of the phage DNA can be readily visualized on agarose gels. This method was used to grossly compare the genomes of nine lactococcal phages isolated from different cheese plants at different times. The method was also used to visualize the inhibitory effects of pTR2030-induced abortive infection on the replication of phage nck202.31 in its homologous host, Lactococcus lactis NCK203. 相似文献
954.
955.
Grzegorz Gajos Aleksander Siniarski Joanna Natorska Michał Ząbczyk Jakub Siudut Krzysztof Piotr Malinowski Renata Gołębiowska-Wiatrak Paweł Rostoff Anetta Undas 《Cardiovascular diabetology》2018,17(1):146
Background
Little is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients.Methods
In 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9–7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro.Results
Polyhedrocytes content in contracted clots was positively correlated with glucose (r?=?0.24, p?=?0.028), glycated hemoglobin (r?=?0.40, p?=?0.024), total cholesterol (r?=?0.22, p?=?0.044), TBARS (r?=?0.60, p?=?0.0027), P-selectin (r?=?0.54, p?=?0.0078) and platelet factor-4, PF4 (r?=?0.59, p?=?0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥?10th percentile) (n?=?83, 85.6%) had higher glucose (+?15.7%, p?=?0.018), fibrinogen (+?16.6%, p?=?0.004), lower red blood cell distribution width (RDW, ??8.8%, p?=?0.034), reduced plasma clot density (??21.8% Ks, p?=?0.011) and impaired fibrinolysis (+?6.5% CLT, p?=?0.037) when compared to patients with lesser amount of polyhedrocytes (<?10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r?=?0.79, p?=?0.036 and r?=?0.67, p?=?0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p?=?0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR?=?0.61, 95% CI 0.39–0.92).Conclusions
Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.956.
Magdalena Markowicz-Piasecka Kristiina M. Huttunen Joanna Sikora 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1309-1322
The aim of this study was to assess in vitro the effects of sulphenamide and sulphonamide derivatives of metformin on the activity of human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), establish the type of inhibition, and assess the potential synergism between biguanides and donepezil towards both cholinesterases (ChEs) and the effects on the β-amyloid aggregation. Sulphonamide 5 with para-trifluoromethyl- and ortho-nitro substituents in aromatic ring inhibited AChE in a mixed-type manner at micromolar concentrations (IC50?=?212.5?±?48.3?µmol/L). The binary mixtures of donepezil and biguanides produce an anti-AChE effect, which was greater than either compound had alone. A combination of donepezil and sulphonamide 5 improved the IC50 value by 170 times. Compound 5 at 200?µmol/L inhibited Aβ aggregation by ~20%. In conclusion, para-trifluoromethyl-ortho-nitro-benzenesulphonamide presents highly beneficial anti-AChE and anti-Aβ aggregation properties which could serve as a promising starting point for the design and development of novel biguanide-based candidates for AD treatment. 相似文献
957.
Jamshed Iqbal Mohammed I. El-Gamal Syeda Abida Ejaz Joanna Lecka Jean Sévigny 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):479-484
Tissue-nonspecific alkaline phosphatase (TNAP) is an important isozyme of alkaline phosphatases, which plays different pivotal roles within the human body. Most importantly, it is responsible for maintaining the balanced ratio of phosphate and inorganic pyrophosphate, thus regulates the extracellular matrix calcification during bone formation and growth. The elevated level of TNAP has been linked to vascular calcification and end-stage renal diseases. Consequently, there is a need to search for highly potent and selective inhibitors of alkaline phosphatases (APs) for treatment of disorders associated with the over-expression of APs. Herein, a series of tricyclic coumarin sulphonate 1a-za with known antiproliferative activity, was evaluated for AP inhibition against human tissue nonspecific alkaline phosphatase (h-TNAP) and human intestinal alkaline phosphatase (h-IAP). The methylbenzenesulphonate derivative 1f (IC50?=?0.38?±?0.01?μM) was found to be the most active h-TNAP inhibitor. Another 4-fluorobenzenesulphonate derivative 1i (IC50?=?0.45?±?0.02?μM) was found as the strongest inhibitor of h-IAP. Some of the derivatives were also identified as highly selective inhibitors of APs. Detailed structure-activity relationship (SAR) was investigated to identify the functional groups responsible for the effective inhibition of AP isozymes. The study was also supported by the docking studies to rationalise the most possible binding site interactions of the identified inhibitors with the targeted enzymes. 相似文献
958.
Assessing uncertainties in crop and pasture ensemble model simulations of productivity and N2O emissions
下载免费PDF全文
![点击此处可从《Global Change Biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Fiona Ehrhardt Jean‐François Soussana Gianni Bellocchi Peter Grace Russel McAuliffe Sylvie Recous Renáta Sándor Pete Smith Val Snow Massimiliano de Antoni Migliorati Bruno Basso Arti Bhatia Lorenzo Brilli Jordi Doltra Christopher D. Dorich Luca Doro Nuala Fitton Sandro J. Giacomini Brian Grant Matthew T. Harrison Stephanie K. Jones Miko U. F. Kirschbaum Katja Klumpp Patricia Laville Joël Léonard Mark Liebig Mark Lieffering Raphaël Martin Raia S. Massad Elizabeth Meier Lutz Merbold Andrew D. Moore Vasileios Myrgiotis Paul Newton Elizabeth Pattey Susanne Rolinski Joanna Sharp Ward N. Smith Lianhai Wu Qing Zhang 《Global Change Biology》2018,24(2):e603-e616
Simulation models are extensively used to predict agricultural productivity and greenhouse gas emissions. However, the uncertainties of (reduced) model ensemble simulations have not been assessed systematically for variables affecting food security and climate change mitigation, within multi‐species agricultural contexts. We report an international model comparison and benchmarking exercise, showing the potential of multi‐model ensembles to predict productivity and nitrous oxide (N2O) emissions for wheat, maize, rice and temperate grasslands. Using a multi‐stage modelling protocol, from blind simulations (stage 1) to partial (stages 2–4) and full calibration (stage 5), 24 process‐based biogeochemical models were assessed individually or as an ensemble against long‐term experimental data from four temperate grassland and five arable crop rotation sites spanning four continents. Comparisons were performed by reference to the experimental uncertainties of observed yields and N2O emissions. Results showed that across sites and crop/grassland types, 23%–40% of the uncalibrated individual models were within two standard deviations (SD) of observed yields, while 42 (rice) to 96% (grasslands) of the models were within 1 SD of observed N2O emissions. At stage 1, ensembles formed by the three lowest prediction model errors predicted both yields and N2O emissions within experimental uncertainties for 44% and 33% of the crop and grassland growth cycles, respectively. Partial model calibration (stages 2–4) markedly reduced prediction errors of the full model ensemble E‐median for crop grain yields (from 36% at stage 1 down to 4% on average) and grassland productivity (from 44% to 27%) and to a lesser and more variable extent for N2O emissions. Yield‐scaled N2O emissions (N2O emissions divided by crop yields) were ranked accurately by three‐model ensembles across crop species and field sites. The potential of using process‐based model ensembles to predict jointly productivity and N2O emissions at field scale is discussed. 相似文献
959.
Vasyl V. Tkach Tyler J. Achatz Joanna Hildebrand Stephen E. Greiman 《Parasitology international》2018,67(4):501-508
The Dicrocoeliidae is a highly diverse family of digeneans parasitic in amniotic tetrapods. Detailed molecular phylogenetic analysis of dicrocoeliids is lacking and only a few dicrocoeliids from mammals have been included in previous studies. Sequence data were previously absent for the Anenterotrematidae that shares several morphological characteristics with dicrocoeliids. We examined phylogenetic affinities of several newly sequenced (nuclear 28S rDNA) taxa of dicrocoeliids and anenterotrematids collected from small mammals in Ecuador, Panama, Peru, USA and Vietnam. Our analyses demonstrated that the two anenterotrematid genera (Anenterotrema, Apharyngotrema) belong to the Dicrocoeliidae, placing the Anenterotrematidae into synonymy with the Dicrocoeliidae. Molecular data combined with morphological examination of type and new specimens provided evidence that Parametadelphis and Apharyngotrema are junior synonyms of Metadelphis, with all Metadelphis species lacking a digestive system. Phylogenetic analysis demonstrates that reduction of the alimentary tract in Lutztrema and its loss in Anenterotrema and Metadelphis represent at least two independent evolutionary events. Genera Brachylecithum, Brachydistomum, and Lyperosomum proved to be non-monophyletic, each likely representing more than a single genus. Furthermore, phylogenetic analysis did not support monophyly of the two largest subfamilies of the Dicrocoeliidae (Dicrocoeliinae and Leipertrematinae) with the other two subfamilies not included in this study. Therefore, we propose to abandon the current subfamily division of the Dicrocoeliidae. Analysis of host associations indicates multiple host-switching events throughout evolution of dicrocoeliids. Lastly, analysis of dicrocoeliid geographic distribution revealed that nearly all major clades included taxa from more than a single zoogeographic realm with the exception of the clade Anenterotrema?+?Metadelphis, found only in the Neotropics. 相似文献
960.
Joanna Bielewicz Anna Szczepańska-Szerej Magdalena Ogórek Piotr Dropko Katarzyna Wojtal Konrad Rejdak 《朊病毒》2018,12(2):143-146
We reported the case of a patient with Wernicke-Korsakoff syndrome (WKs) as an early clinical manifestation of sporadic Creutzfeld-Jakob disease (sCJD). The 66-year-old female complained of dizziness and imbalance which mostly occurred while walking. A neurological examination revealed a triad of symptoms characteristic for WKs such as gaze paresis, ataxia of limbs and trunk as well as memory disturbances with confabulations. The disturbances increased during the course of the disease, which led to the death of the patient four months after the appearance of the signs. The patient was finally diagnosed with sCJD disease. The most useful ancillary examination results supporting sCJD diagnosis were brain diffusion DWI MRI (diffusion weighted magnetic resonance imaging) and the presence of 14–3-3 protein in CSF (cerebrospinal fluid). Since that manifestation of sCJD is very unique other causes should be taken into consideration while making a final diagnosis. 相似文献