全文获取类型
收费全文 | 2805篇 |
免费 | 198篇 |
专业分类
3003篇 |
出版年
2023年 | 16篇 |
2022年 | 22篇 |
2021年 | 33篇 |
2020年 | 39篇 |
2019年 | 36篇 |
2018年 | 44篇 |
2017年 | 35篇 |
2016年 | 81篇 |
2015年 | 121篇 |
2014年 | 141篇 |
2013年 | 145篇 |
2012年 | 213篇 |
2011年 | 192篇 |
2010年 | 130篇 |
2009年 | 99篇 |
2008年 | 162篇 |
2007年 | 157篇 |
2006年 | 142篇 |
2005年 | 141篇 |
2004年 | 144篇 |
2003年 | 144篇 |
2002年 | 144篇 |
2001年 | 41篇 |
2000年 | 24篇 |
1999年 | 24篇 |
1998年 | 51篇 |
1997年 | 34篇 |
1996年 | 22篇 |
1995年 | 30篇 |
1994年 | 25篇 |
1993年 | 26篇 |
1992年 | 32篇 |
1991年 | 17篇 |
1990年 | 20篇 |
1989年 | 14篇 |
1988年 | 21篇 |
1987年 | 22篇 |
1986年 | 18篇 |
1985年 | 12篇 |
1984年 | 12篇 |
1982年 | 11篇 |
1981年 | 23篇 |
1980年 | 15篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1972年 | 6篇 |
1969年 | 6篇 |
1968年 | 7篇 |
排序方式: 共有3003条查询结果,搜索用时 15 毫秒
81.
Marianne Skeie Filip Nikolaysen Ylenia Chitano Espen Stang 《Journal of cellular and molecular medicine》2020,24(17):10258-10262
The receptor tyrosine kinase HER2 is associated with a number of human malignancies and is an important therapeutic target. The antibody‐drug conjugate trastuzumab emtansine (T‐DM1; Kadcyla®) is recommended as a first‐line treatment for patients with HER2‐positive metastatic breast cancer. T‐DM1 combines the antibody‐induced effects of the anti‐HER2 antibody trastuzumab (Herceptin®) with the cytotoxic effect of the tubulin inhibitor mertansine (DM1). For DM1 to have effect, the T‐DM1‐HER2 complex has to be internalized and the trastuzumab part of T‐DM1 has to be degraded. HER2 is, however, considered endocytosis‐resistant. As a result of this, trastuzumab is only internalized to a highly limited extent, and if internalized, it is rapidly recycled. The exact reasons for the endocytosis resistance of HER2 are not clear, but it is stabilized by heat‐shock protein 90 (Hsp90) and Hsp90 inhibitors induce internalization and degradation of HER2. HER2 can also be internalized upon activation of protein kinase C, and contrary to trastuzumab alone, the combination of two or more anti‐HER2 antibodies can induce efficient internalization and degradation of HER2. With intention to find ways to improve the action of T‐DM1, we investigated how different ways of inducing HER2 internalization leads to degradation of trastuzumab. The results show that although both Hsp90 inhibition and activation of protein kinase C induce internalization of trastuzumab, only Hsp90 inhibition induces degradation. Furthermore, we find that antibody internalization and degradation are increased when trastuzumab is combined with the clinically approved anti‐HER2 antibody pertuzumab (Perjeta®). 相似文献
82.
Mnica Arias Marianne Elias Christine Andraud Serge Berthier Doris Gomez 《Journal of evolutionary biology》2020,33(2):247-252
Predation is a ubiquitous and strong selective pressure on living organisms. Transparency is a predation defence widespread in water but rare on land. Some Lepidoptera display transparent patches combined with already cryptic opaque patches. A recent study showed that transparency reduced detectability of aposematic prey with conspicuous patches. However, whether transparency has any effect at reducing detectability of already cryptic prey is still unknown. We conducted field predation experiments with free avian predators where we monitored and compared survival of a fully opaque grey artificial form (cryptic), a form including transparent windows and a wingless artificial butterfly body. Survival of the transparent forms was similar to that of wingless bodies and higher than that of fully opaque forms, suggesting a reduction of detectability conferred by transparency. This is the first evidence that transparency decreases detectability in cryptic terrestrial prey. Future studies should explore the organization of transparent and opaque patches in animals and their interplay on survival, as well as the costs and other potential benefits associated with transparency on land. 相似文献
83.
Laurne Mrillet Dorothe Kopp Marianne Robert Maud Mouchet Sandrine Pavoine 《Global Change Biology》2020,26(4):2106-2119
Global climate change has already caused bottom temperatures of coastal marine ecosystems to increase worldwide. These ecosystems face many pressures, of which fishing is one of the most important. While consequences of global warming on commercial species are studied extensively, the importance of the increase in bottom temperature and of variation in fishing effort is more rarely considered together in these exploited ecosystems. Using a 17 year time series from an international bottom trawl survey, we investigated covariations of an entire demersal ecosystem (101 taxa) with the environment in the Celtic Sea. Our results showed that over the past two decades, biotic communities in the Celtic Sea were likely controlled more by environmental variables than fisheries, probably due to its long history of exploitation. At the scale of the entire zone, relations between taxa and the environment remained stable over the years, but at a local scale, in the center of the Celtic Sea, dynamics were probably driven by interannual variation in temperature. Fishing was an important factor structuring species assemblages at the beginning of the time series (2000) but decreased in importance after 2009. This was most likely caused by a change in spatial distribution of fishing effort, following a change in targeted taxa from nephrops to deeper water anglerfish that did not covary with fishing effort. Increasing bottom temperatures could induce additional changes in the coming years, notably in the cold‐water commercial species cod, hake, nephrops, and American plaice. We showed that analyzing covariation is an effective way to screen a large number of taxa and highlight those that may be most susceptible to future simultaneous increases in temperature and changes in exploitation pattern by fisheries. This information can be particularly relevant for ecosystem assessments. 相似文献
84.
85.
Morales-Molino César Steffen Marianne Samartin Stéphanie van Leeuwen Jaqueline F. N. Hürlimann Daniel Vescovi Elisa Tinner Willy 《Ecosystems》2021,24(6):1361-1377
Ecosystems - Fagus sylvatica (beech) dominates the montane forests of the Apennines and builds old-growth high-conservation value stands. However, recent severe drought-induced diebacks raise... 相似文献
86.
Nicole Wüppenhorst Friederike von Loewenich Beate Hobmaier Marianne Vetter‐Knoll Sona Mohadjer Manfred Kist 《Helicobacter》2013,18(1):1-5
Helicobacter felis belongs to the fastidious gastric non‐Helicobacter pylori helicobacter species that are typically found in the stomach of cats and dogs. These bacteria have the potential to colonize the human stomach and are then associated with gastritis, gastroduodenal ulcers, and MALT lymphoma. Strains cultured from the human stomach are rare. Here, we present the first isolation of H. felis from a gastric biopsy specimen of a 14‐year‐old girl who presented with persistent epigastric pain. The strain was cultured using our routine protocol for H. pylori and identified by phylogenetic analyses of partial urease AB and gyrB gene sequences. 相似文献
87.
Brian A. Otter Shirish A. Patil Marianne R. Spada Linda A. Jelicks Yuichi Yoshimura Akira Matsuda 《Nucleosides, nucleotides & nucleic acids》2013,32(2-4):615-635
Abstract The 5-oxo-6-methylene-pyrimidine-2,4-dione intermediate (6) that is formed when 5-acetoxy-6-acetoxymethyl-1-β-D-(5-O-acetyl-2,3-O-isopropylidene)-ribofuranosyluracil (5) is treated with sodium hydroxide undergoes cyclization at pH 14 to give 2′,3′-O-isopropylidene-5-hydroxy- O 5, 6-methanouridine (8) in good yield. Conversion of 8 into the 5-triflate ester 14 followed by reduction with [(Ph)3P]4Pd/Bu3SnH and deblocking with acetic acid then affords O 5′, 6-methanouridine (4) Conformational studies (NOE difference spectra, vicinal 1H-13C coupling constants, NOESY and CD spectra, molecular modeling) indicate that the C7-methylene group of 4 projects towards the furanose ring oxygen atom, producing a glycosyl rotation angle of about ? 160°. 相似文献
88.
Altered expression of the PTR/NRT1 homologue OsPTR9 affects nitrogen utilization efficiency,growth and grain yield in rice 总被引:2,自引:0,他引:2
Zhongming Fang Kuaifei Xia Xin Yang Marianne Suter Grotemeyer Stefan Meier Doris Rentsch Xinlan Xu Mingyong Zhang 《Plant biotechnology journal》2013,11(4):446-458
The plant PTR/NRT1 (peptide transporter/nitrate transporter 1) gene family comprises di/tripeptide and low‐affinity nitrate transporters; some members also recognize other substrates such as carboxylates, phytohormones (auxin and abscisic acid), or defence compounds (glucosinolates). Little is known about the members of this gene family in rice (Oryza sativa L.). Here, we report the influence of altered OsPTR9 expression on nitrogen utilization efficiency, growth, and grain yield. OsPTR9 expression is regulated by exogenous nitrogen and by the day‐night cycle. Elevated expression of OsPTR9 in transgenic rice plants resulted in enhanced ammonium uptake, promotion of lateral root formation and increased grain yield. On the other hand, down‐regulation of OsPTR9 in a T‐DNA insertion line (osptr9) and in OsPTR9‐RNAi rice plants had the opposite effect. These results suggest that OsPTR9 might hold potential for improving nitrogen utilization efficiency and grain yield in rice breeding. 相似文献
89.
The human liver ATP-binding cassette (ABC) transporters bile salt export pump (BSEP/ABCB11) and the multidrug resistance protein 3 (MDR3/ABCB4) fulfill the translocation of bile salts and phosphatidylcholine across the apical membrane of hepatocytes. In concert with ABCG5/G8, these two transporters are responsible for the formation of bile and mutations within these transporters can lead to severe hereditary diseases. In this study, we report the heterologous overexpression and purification of human BSEP and MDR3 as well as the expression of the corresponding C-terminal GFP-fusion proteins in the yeast Pichia pastoris. Confocal laser scanning microscopy revealed that BSEP-GFP and MDR3-GFP are localized in the plasma membrane of P. pastoris. Furthermore, we demonstrate the first purification of human BSEP and MDR3 yielding ∼1 mg and ∼6 mg per 100 g of wet cell weight, respectively. By screening over 100 detergents using a dot blot technique, we found that only zwitterionic, lipid-like detergents such as Fos-cholines or Cyclofos were able to extract both transporters in sufficient amounts for subsequent functional analysis. For MDR3, fluorescence-detection size exclusion chromatography (FSEC) screens revealed that increasing the acyl chain length of Fos-Cholines improved monodispersity. BSEP purified in n-dodecyl-β-D-maltoside or Cymal-5 after solubilization with Fos-choline 16 from P. pastoris membranes showed binding to ATP-agarose. Furthermore, detergent-solubilized and purified MDR3 showed a substrate-inducible ATPase activity upon addition of phosphatidylcholine lipids. These results form the basis for further biochemical analysis of human BSEP and MDR3 to elucidate the function of these clinically relevant ABC transporters. 相似文献
90.
Nicole H. T. M. Dukers-Muijrers Arjen G. C. L. Speksnijder Servaas A. Morré Petra F. G. Wolffs Marianne A. B. van der Sande Antoinette A. T. P. Brink Ingrid V. F. van den Broek Marita I. L. S. Werner Christian J. P. A. Hoebe 《PloS one》2013,8(11)