全文获取类型
收费全文 | 3912篇 |
免费 | 332篇 |
国内免费 | 2篇 |
专业分类
4246篇 |
出版年
2023年 | 19篇 |
2022年 | 29篇 |
2021年 | 58篇 |
2020年 | 34篇 |
2019年 | 40篇 |
2018年 | 83篇 |
2017年 | 53篇 |
2016年 | 91篇 |
2015年 | 162篇 |
2014年 | 205篇 |
2013年 | 200篇 |
2012年 | 291篇 |
2011年 | 259篇 |
2010年 | 174篇 |
2009年 | 156篇 |
2008年 | 220篇 |
2007年 | 240篇 |
2006年 | 208篇 |
2005年 | 220篇 |
2004年 | 172篇 |
2003年 | 206篇 |
2002年 | 176篇 |
2001年 | 41篇 |
2000年 | 29篇 |
1999年 | 32篇 |
1998年 | 46篇 |
1997年 | 37篇 |
1996年 | 31篇 |
1995年 | 30篇 |
1994年 | 22篇 |
1993年 | 27篇 |
1992年 | 15篇 |
1991年 | 30篇 |
1990年 | 39篇 |
1989年 | 23篇 |
1988年 | 30篇 |
1987年 | 26篇 |
1986年 | 16篇 |
1985年 | 17篇 |
1984年 | 22篇 |
1983年 | 19篇 |
1982年 | 22篇 |
1981年 | 24篇 |
1980年 | 19篇 |
1978年 | 15篇 |
1977年 | 16篇 |
1974年 | 14篇 |
1969年 | 13篇 |
1968年 | 13篇 |
1967年 | 15篇 |
排序方式: 共有4246条查询结果,搜索用时 11 毫秒
51.
Catharina I. Delebinski Monika Twardziok Susann Kleinsimon Florian Hoff Katharina Mulsow Jana Rolff Sebastian J?ger Angelika Eggert Georg Seifert 《PloS one》2015,10(8)
Aqueous Viscum album L. extracts are widely used in complementary cancer medicine. Hydrophobic triterpene acids also possess anti-cancer properties, but due to their low solubility they do not occur in significant amounts in aqueous extracts. Using cyclodextrins we solubilised mistletoe triterpenes (mainly oleanolic acid) and investigated the effect of a mistletoe whole plant extract on human acute myeloid leukaemia cells in vitro, ex vivo and in vivo. Single Viscum album L. extracts containing only solubilised triterpene acids (TT) or lectins (viscum) inhibited cell proliferation and induced apoptosis in a dose-dependent manner in vitro and ex vivo. The combination of viscum and TT extracts (viscumTT) enhanced the induction of apoptosis synergistically. The experiments demonstrated that all three extracts are able to induce apoptosis via caspase-8 and -9 dependent pathways with down-regulation of members of the inhibitor of apoptosis and Bcl-2 families of proteins. Finally, the acute myeloid leukaemia mouse model experiment confirmed the therapeutic effectiveness of viscumTT-treatment resulting in significant tumour weight reduction, comparable to the effect in cytarabine-treated mice. These results suggest that the combination viscumTT may have a potential therapeutic value for the treatment AML. 相似文献
52.
Franziska Heidemann Anna Schildt Katharina Schmid Oliver T. Bruns Kristoffer Riecken Caroline Jung Harald Ittrich Daniel Wicklein Rudolph Reimer Boris Fehse Joerg Heeren Georg Lüers Udo Schumacher Markus Heine 《PloS one》2014,9(4)
Metastasis formation is the major reason for the extremely poor prognosis in small cell lung cancer (SCLC) patients. The molecular interaction partners regulating metastasis formation in SCLC are largely unidentified, however, from other tumor entities it is known that tumor cells use the adhesion molecules of the leukocyte adhesion cascade to attach to the endothelium at the site of the future metastasis. Using the human OH-1 SCLC line as a model, we found that these cells expressed E- and P-selectin binding sites, which could be in part attributed to the selectin binding carbohydrate motif sialyl Lewis A. In addition, protein backbones known to carry these glycotopes in other cell lines including PSGL-1, CD44 and CEA could be detected in in vitro and in vivo grown OH1 SCLC cells. By intravital microscopy of murine mesenterial vasculature we could capture SCLC cells while rolling along vessel walls demonstrating that SCLC cells mimic leukocyte rolling behavior in terms of selectin and selectin ligand interaction in vivo indicating that this mechanism might indeed be important for SCLC cells to seed distant metastases. Accordingly, formation of spontaneous distant metastases was reduced by 50% when OH-1 cells were xenografted into E-/P-selectin-deficient mice compared with wild type mice (p = 0.0181). However, as metastasis formation was not completely abrogated in selectin deficient mice, we concluded that this adhesion cascade is redundant and that other molecules of this cascade mediate metastasis formation as well. Using several of these adhesion molecules as interaction partners presumably make SCLC cells so highly metastatic. 相似文献
53.
Otte Kathrin A. Effertz Christoph Fröhlich Thomas Arnold Georg J. Laforsch Christian von Elert Eric 《Hydrobiologia》2019,846(1):27-38
Hydrobiologia - The crustacean genus Daphnia holds a key position in aquatic ecosystems rendering it an important model organism in environmental research. Its enormous sensitivity to environmental... 相似文献
54.
Gaj P Maryan N Hennig EE Ledwon JK Paziewska A Majewska A Karczmarski J Nesteruk M Wolski J Antoniewicz AA Przytulski K Rutkowski A Teumer A Homuth G Starzyńska T Regula J Ostrowski J 《PloS one》2012,7(4):e35307
Background
Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations.Methods
To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ2-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r2>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays.Results
The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction.Conclusion
Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci. 相似文献55.
56.
Georg Terler Leonhard Gruber Wilhelm Friedrich Knaus 《Archives of animal nutrition》2017,71(5):333-346
The nutritive value of whole crop forage maize is influenced by the proportion of ears and stover in the whole crop and by the nutrient composition and digestibility characteristics of the plant parts. An experiment investigating the impact of variety, harvest date and year on the nutritive value of ensiled maize ears was carried out in three consecutive years (2007, 2008 and 2010). Nine different maize varieties were harvested at three different maturity stages (50, 55 and 60% dry matter (DM) content in the ears). After harvest, ears and stover were ensiled separately and afterwards nutrient composition and ruminal nutrient degradability (organic matter (OM), crude protein (CP) and non-fibre carbohydrates (NFC)) were analysed. Variety had a significant influence on content of CP and effective ruminal degradability (ED) of OM at low passage rates, whereas ED of CP and NFC was not affected by variety. In contrast, harvest date and year significantly influenced nutrient composition and ruminal degradability of ensiled maize ears. The content of NFC increased and the content of fibre components as well as ED of OM, CP and NFC declined with processing maturity of the maize plants. At a passage rate of 5% h?1, ED of OM declined from 75.9% to 68.4%, ED of CP from 82.5% to 73.8% and ED of NFC from 88.0% to 82.3% between the early and late harvest date. The results of this study indicate that the nutrient composition and ruminal degradability of ensiled maize ears are affected mainly by maturity stage at harvest and by year, whereas variety has only little influence. 相似文献
57.
Peter Braubach Murat Orynbayev Zoita Andronache Tanja Hering Georg Bernhard Landwehrmeyer Katrin S. Lindenberg Werner Melzer 《The Journal of general physiology》2014,144(5):393-413
Huntington’s disease (HD) is caused by an expanded CAG trinucleotide repeat within the gene encoding the protein huntingtin. The resulting elongated glutamine (poly-Q) sequence of mutant huntingtin (mhtt) affects both central neurons and skeletal muscle. Recent reports suggest that ryanodine receptor–based Ca2+ signaling, which is crucial for skeletal muscle excitation–contraction coupling (ECC), is changed by mhtt in HD neurons. Consequently, we searched for alterations of ECC in muscle fibers of the R6/2 mouse, a mouse model of HD. We performed fluorometric recordings of action potentials (APs) and cellular Ca2+ transients on intact isolated toe muscle fibers (musculi interossei), and measured L-type Ca2+ inward currents on internally dialyzed fibers under voltage-clamp conditions. Both APs and AP-triggered Ca2+ transients showed slower kinetics in R6/2 fibers than in fibers from wild-type mice. Ca2+ removal from the myoplasm and Ca2+ release flux from the sarcoplasmic reticulum were characterized using a Ca2+ binding and transport model, which indicated a significant reduction in slow Ca2+ removal activity and Ca2+ release flux both after APs and under voltage-clamp conditions. In addition, the voltage-clamp experiments showed a highly significant decrease in L-type Ca2+ channel conductance. These results indicate profound changes of Ca2+ turnover in skeletal muscle of R6/2 mice and suggest that these changes may be associated with muscle pathology in HD. 相似文献
58.
Cytoplasmic thioredoxin reductase is essential for embryogenesis but dispensable for cardiac development 下载免费PDF全文
Jakupoglu C Przemeck GK Schneider M Moreno SG Mayr N Hatzopoulos AK de Angelis MH Wurst W Bornkamm GW Brielmeier M Conrad M 《Molecular and cellular biology》2005,25(5):1980-1988
Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and the mitochondria of mammalian cells. Thioredoxins (Txn), the main substrates of thioredoxin reductases (Txnrd), are involved in numerous physiological processes, including cell-cell communication, redox metabolism, proliferation, and apoptosis. To investigate the individual contribution of mitochondrial (Txnrd2) and cytoplasmic (Txnrd1) thioredoxin reductases in vivo, we generated a mouse strain with a conditionally targeted deletion of Txnrd1. We show here that the ubiquitous Cre-mediated inactivation of Txnrd1 leads to early embryonic lethality. Homozygous mutant embryos display severe growth retardation and fail to turn. In accordance with the observed growth impairment in vivo, Txnrd1-deficient embryonic fibroblasts do not proliferate in vitro. In contrast, ex vivo-cultured embryonic Txnrd1-deficient cardiomyocytes are not affected, and mice with a heart-specific inactivation of Txnrd1 develop normally and appear healthy. Our results indicate that Txnrd1 plays an essential role during embryogenesis in most developing tissues except the heart. 相似文献
59.
60.
Changes in plant species richness over the last century in the eastern Swiss Alps: elevational gradient, bedrock effects and migration rates 总被引:2,自引:0,他引:2
Areas of 2,800–3,000 m a.s.l. represent the alpine-nival ecotone in the Alps. This transition zone connecting the closed swards
of the alpine belt and the scattered vegetation of the nival belt may show particularly strong climate warming driven fluctuations
in plant species richness compared to the nival belt. To test this hypothesis, 12 summits within this range were investigated
in the canton of Grisons, Switzerland in 2004. Complete lists of vascular plant species consisting of 5–70 species were collected
on each summit and the elevation of the uppermost occurrence of each species was recorded. These data were compared to historical
records over 120 years in age. Within this time, vascular plant species richness increased by 11% per decade on summits in
the alpine-nival ecotone. Despite this considerable change, a comparison with nival summits did not support the hypothesis
that species richness increase at the alpine-nival ecotone is higher than in the nival belt. A general trend of upward migration
in the range of several metres per decade could be observed. Anemochorous species were more often found to be migrating than
zoochorous or autochorous species and migration was higher on calcareous than on siliceous bedrock. A comparison between the
summits with the adjacent slopes in our study revealed that changes in species number could be used as an indicator for climate-induced
changes—if at all—only for the narrow summit areas. 相似文献