全文获取类型
收费全文 | 1071篇 |
免费 | 90篇 |
专业分类
1161篇 |
出版年
2020年 | 9篇 |
2018年 | 10篇 |
2016年 | 18篇 |
2015年 | 23篇 |
2014年 | 31篇 |
2013年 | 36篇 |
2012年 | 46篇 |
2011年 | 56篇 |
2010年 | 44篇 |
2009年 | 26篇 |
2008年 | 32篇 |
2007年 | 36篇 |
2006年 | 32篇 |
2005年 | 35篇 |
2004年 | 35篇 |
2003年 | 38篇 |
2002年 | 25篇 |
2001年 | 36篇 |
2000年 | 33篇 |
1999年 | 29篇 |
1998年 | 17篇 |
1997年 | 9篇 |
1996年 | 12篇 |
1995年 | 16篇 |
1993年 | 10篇 |
1992年 | 17篇 |
1991年 | 18篇 |
1990年 | 26篇 |
1989年 | 18篇 |
1988年 | 18篇 |
1987年 | 24篇 |
1986年 | 17篇 |
1985年 | 24篇 |
1984年 | 10篇 |
1983年 | 16篇 |
1982年 | 17篇 |
1981年 | 10篇 |
1980年 | 10篇 |
1979年 | 21篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1976年 | 16篇 |
1975年 | 14篇 |
1974年 | 17篇 |
1973年 | 21篇 |
1972年 | 12篇 |
1971年 | 11篇 |
1970年 | 10篇 |
1968年 | 9篇 |
1966年 | 8篇 |
排序方式: 共有1161条查询结果,搜索用时 14 毫秒
91.
The mitochondrial genome of the stramenopile alga Chrysodidymus synuroideus. Complete sequence, gene content and genome organization
下载免费PDF全文
![点击此处可从《Nucleic acids research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Chesnick JM Goff M Graham J Ocampo C Lang BF Seif E Burger G 《Nucleic acids research》2000,28(13):2512-2518
This is the first report of a complete mitochondrial genome sequence from a photosynthetic member of the stramenopiles, the chrysophyte alga Chrysodidymus synuroideus. The circular-mapping mitochondrial DNA (mtDNA) of 34 119 bp contains 58 densely packed genes (all without introns) and five unique open reading frames (ORFs). Protein genes code for components of respiratory chain complexes, ATP synthase and the mitoribosome, as well as one product of unknown function, encoded in many other protist mtDNAs (YMF16). In addition to small and large subunit ribosomal RNAs, 23 tRNAs are mtDNA-encoded, permitting translation of all codons present in protein-coding genes except ACN (Thr) and CGN (Arg). The missing tRNAs are assumed to be imported from the cytosol. Comparison of the C.synuroideus mtDNA with that of other stramenopiles allowed us to draw conclusions about mitochondrial genome organization, expression and evolution. First, we provide evidence that mitochondrial ORFs code for highly derived, unrecognizable versions of ribosomal or respiratory genes otherwise ‘missing’ in a particular mtDNA. Secondly, the observed constraints in mitochondrial genome rearrangements suggest operon-based, co-ordinated expression of genes functioning in common biological processes. Finally, stramenopile mtDNAs reveal an unexpectedly low variability in genome size and gene complement, testifying to substantial differences in the tempo of mtDNA evolution between major eukaryotic lineages. 相似文献
92.
Mechanical loading-induced fluid flow in the lacuno-canalicular network is a possible signal for bone cell adaptive responses. In an earlier study we found that pulsating fluid flow (PFF, 0.7+/-0.02 Pa, 5 Hz, 0.4 Pa/s) stimulates the production of prostaglandins by neonatal mouse calvarial cells. In addition, mRNA expression of the inducible form of cyclooxygenase (COX-2), but not the constitutive form (COX-1), the major enzymes in prostaglandin production, was increased by PFF. The present study was performed to determine whether human primary bone cells from the iliac crest, respond to mechanical stress in a similar way as neonatal mouse calvarial cells. We subjected bone cells originating from the iliac crest of nine elderly women, between 56 and 80 yr of age, for 1 h to PFF and measured prostaglandin production and COX-1 and COX-2 mRNA expression. One hour PFF treatment stimulated the release of PGE2 by 3.5 fold and PGI2 by 2.2 fold. PFF also increased the expression of COX-2 mRNA by 2.9 fold, but did not change COX-1 mRNA. No correlation was found between donor age and PFF effect, neither on prostaglandin production nor on COX-2 mRNA expression. This study shows that bone cells from the iliac crest of elderly women react to PFF treatment in a similar way as neonatal mouse calvarial cells, namely with increased production of prostaglandins and upregulation of COX-2 mRNA expression. These results suggest that human bone cells from the iliac crest and neonatal mouse calvarial cells share a similar mechanotransduction pathway. 相似文献
93.
Burger H Capello A Schenk PW Stoter G Brouwer J Nooter K 《Biochemical and biophysical research communications》2000,269(3):767-774
Cisplatin is a potent DNA-damaging agent that has demonstrated anticancer activities against several tumors. However, manifestation of cellular resistance is a major obstacle in anticancer therapy that severely limits the curative potential of cisplatin. Therefore, understanding the molecular basis of cisplatin resistance could significantly improve the clinical efficacy of this anticancer agent. Here, we employed Saccharomyces cerevisiae as a model organism to study cisplatin resistance mechanisms and describe a one-step cisplatin selection to identify and characterize novel cisplatin resistance genes. Screening a multicopy yeast genomic library enabled us to isolate several yeast clones for which we could confirm that the cisplatin resistance phenotype was linked to the introduced fragment. In a first attempt, a number of open reading frames could be identified. Among these genes, PDE2 and ZDS2 were repeatedly identified as genes whose overexpression confers cellular resistance to cisplatin. PDE2, encoding cAMP-phosphodiesterase 2, is of particular interest because the overexpression of this yeast gene is known to induce cisplatin resistance in mammalian cells as well, providing proof of the principle of our experimental approach. In addition, the identification of PDE2 shows that our yeast screening system can directly be informative for drug resistance in mammalian cells. 相似文献
94.
Simon C Herling AW Preibisch G Burger HJ 《Archives of biochemistry and biophysics》2000,373(2):418-428
The multicomponent hepatic glucose 6-phosphatase (Glc-6-Pase) system catalyzes the terminal step of hepatic glucose production and plays a key role in the regulation of blood glucose. We used the chlorogenic acid derivative S 3483, a reversible inhibitor of the glucose-6-phosphate (Glc-6-P) translocase component, to demonstrate for the first time upregulation of Glc-6-Pase expression in rat liver in vivo after inhibition of Glc-6-P translocase. In accordance with its mode of action, S 3483-treatment of overnight-fasted rats induced hypoglycemia and increased blood lactate, hepatic Glc-6-P, and glycogen. The metabolic changes were accompanied by rapid and marked increases in Glc-6-Pase mRNA (above 35-fold), protein (about 2-fold), and enzymatic activity (about 2-fold). Maximal mRNA levels were reached after 4 h of treatment. Glycemia, blood lactate, and Glc-6-Pase mRNA levels returned to control values, whereas Glc-6-P and glycogen levels decreased but were still elevated 2 h after S 3483 withdrawal. The capacity for Glc-6-P influx was only marginally increased after 8.5 h of treatment. Prevention of hypoglycemia by euglycemic clamp did not abolish the increase in Glc-6-Pase mRNA induced by S 3483 treatment. A similar pattern of hypoglycemia and possibly of associated counterregulatory responses elicited by treatment with the phosphoenolpyruvate carboxykinase inhibitor 3-mercaptopicolinic acid could account for only a 2-fold induction of Glc-6-Pase mRNA. These findings suggest that the significant upregulation of Glc-6-Pase gene expression observed after treatment of rats in vivo with an inhibitor of Glc-6-P translocase is caused predominantly either by S 3483 per se or by the compound-induced changes of intracellular carbohydrate metabolism. 相似文献
95.
Hans J. Maree Michael D. Pirie Kristin Oosthuizen Rachelle Bester D. Jasper G. Rees Johan T. Burger 《PloS one》2015,10(5)
The evolutionary history of the exclusively grapevine (Vitis spp.) infecting, grapevine leafroll-associated virus 3 (GLRaV-3) has not been studied extensively, partly due to limited available sequence data. In this study we trace the evolutionary history of GLRaV-3, focussing on isolate GH24, a newly discovered variant. GH24 was discovered through the use of next-generation sequencing (NGS) and the whole genome sequence determined and validated with Sanger sequencing. We assembled an alignment of all 13 available whole genomes of GLRaV-3 isolates and all other publicly available GLRaV-3 sequence data. Using multiple recombination detection methods we identified a clear signal for recombination in one whole genome sequence and further evidence for recombination in two more, including GH24. We inferred phylogenetic trees and networks and estimated the ages of common ancestors of GLRaV-3 clades by means of relaxed clock models calibrated with asynchronous sampling dates. Our results generally confirm previously identified variant groups as well as two new groups (VII and VIII). Higher order groups were defined as supergroups designated A to D. Supergroup A includes variant groups I-V and supergroup B group VI and its related unclassified isolates. Supergroups C and D are less well known, including the newly identified groups VII (including isolate GH24) and VIII respectively. The inferred node ages suggest that the origins of the major groups of GLRaV-3, including isolate GH24, may have occurred prior to worldwide cultivation of grapevines, whilst the current diversity represents closely related isolates that diverged from common ancestors within the last century. 相似文献
96.
The size of the human population is relevant to the development of a sustainable world, yet the forces setting growth or declines in the human population are poorly understood. Generally, population growth rates depend on whether new individuals compete for the same energy (leading to Malthusian or density-dependent growth) or help to generate new energy (leading to exponential and super-exponential growth). It has been hypothesized that exponential and super-exponential growth in humans has resulted from carrying capacity, which is in part determined by energy availability, keeping pace with or exceeding the rate of population growth. We evaluated the relationship between energy use and population size for countries with long records of both and the world as a whole to assess whether energy yields are consistent with the idea of an increasing carrying capacity. We find that on average energy use has indeed kept pace with population size over long time periods. We also show, however, that the energy-population scaling exponent plummets during, and its temporal variability increases preceding, periods of social, political, technological, and environmental change. We suggest that efforts to increase the reliability of future energy yields may be essential for stabilizing both population growth and the global socio-economic system. 相似文献
97.
Jacob H. Lowenstein Joanna Burger Christian W. Jeitner George Amato Sergios-Orestis Kolokotronis Michael Gochfeld 《Biology letters》2010,6(5):692-695
Excessive ingestion of mercury—a health hazard associated with consuming predatory fishes—damages neurological, sensory-motor and cardiovascular functioning. The mercury levels found in Bigeye Tuna (Thunnus obesus) and bluefin tuna species (Thunnus maccoyii, Thunnus orientalis, and Thunnus thynnus), exceed or approach levels permissible by Canada, the European Union, Japan, the US, and the World Health Organization. We used DNA barcodes to identify tuna sushi samples analysed for mercury and demonstrate that the ability to identify cryptic samples in the market place allows regulatory agencies to more accurately measure the risk faced by fish consumers and enact policies that better safeguard their health. 相似文献
98.
A genetic map of melon highly enriched with fruit quality QTLs and EST markers, including sugar and carotenoid metabolism genes 总被引:4,自引:0,他引:4
R. Harel-Beja G. Tzuri V. Portnoy M. Lotan-Pompan S. Lev S. Cohen N. Dai L. Yeselson A. Meir S. E. Libhaber E. Avisar T. Melame P. van Koert H. Verbakel R. Hofstede H. Volpin M. Oliver A. Fougedoire C. Stalh J. Fauve B. Copes Z. Fei J. Giovannoni N. Ori E. Lewinsohn A. Sherman J. Burger Y. Tadmor A. A. Schaffer N. Katzir 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2010,121(3):511-533
A genetic map of melon enriched for fruit traits was constructed, using a recombinant inbred (RI) population developed from a cross between representatives of the two subspecies of Cucumis melo L.: PI 414723 (subspecies agrestis) and ‘Dulce’ (subspecies melo). Phenotyping of 99 RI lines was conducted over three seasons in two locations in Israel and the US. The map includes 668 DNA markers (386 SSRs, 76 SNPs, six INDELs and 200 AFLPs), of which 160 were newly developed from fruit ESTs. These ESTs include candidate genes encoding for enzymes of sugar and carotenoid metabolic pathways that were cloned from melon cDNA or identified through mining of the International Cucurbit Genomics Initiative database (http://www.icugi.org/). The map covers 1,222 cM with an average of 2.672 cM between markers. In addition, a skeleton physical map was initiated and 29 melon BACs harboring fruit ESTs were localized to the 12 linkage groups of the map. Altogether, 44 fruit QTLs were identified: 25 confirming QTLs described using other populations and 19 newly described QTLs. The map includes QTLs for fruit sugar content, particularly sucrose, the major sugar affecting sweetness in melon fruit. Six QTLs interacting in an additive manner account for nearly all the difference in sugar content between the two genotypes. Three QTLs for fruit flesh color and carotenoid content were identified. Interestingly, no clear colocalization of QTLs for either sugar or carotenoid content was observed with over 40 genes encoding for enzymes involved in their metabolism. The RI population described here provides a useful resource for further genomics and metabolomics studies in melon, as well as useful markers for breeding for fruit quality. 相似文献
99.
Mariana Pehar Kenneth J. O’Riordan Melissa Burns‐Cusato Matthew E. Andrzejewski Carlos Gil Del Alcazar Corinna Burger Heidi Scrable Luigi Puglielli 《Aging cell》2010,9(2):174-190
The longevity‐assurance activity of the tumor suppressor p53 depends on the levels of Δ40p53 (p44), a short and naturally occurring isoform of the p53 gene. As such, increased dosage of p44 in the mouse leads to accelerated aging and short lifespan. Here we show that mice homozygous for a transgene encoding p44 (p44+/+) display cognitive decline and synaptic impairment early in life. The synaptic deficits are attributed to hyperactivation of insulin‐like growth factor 1 receptor (IGF‐1R) signaling and altered metabolism of the microtubule‐binding protein tau. In fact, they were rescued by either Igf1r or Mapt haploinsufficiency. When expressing a human or a ‘humanized’ form of the amyloid precursor protein (APP), p44+/+ animals developed a selective degeneration of memory‐forming and ‐retrieving areas of the brain, and died prematurely. Mechanistically, the neurodegeneration was caused by both paraptosis‐ and autophagy‐like cell deaths. These results indicate that altered longevity‐assurance activity of p53:p44 causes memory loss and neurodegeneration by affecting IGF‐1R signaling. Importantly, Igf1r haploinsufficiency was also able to correct the synaptic deficits of APP695/swe mice, a model of Alzheimer’s disease. 相似文献
100.
Anna Scanu Francesca Oliviero Lyssia Gruaz Paolo Sfriso Assunta Pozzuoli Federica Frezzato Carlo Agostini Danielle Burger Leonardo Punzi 《Arthritis research & therapy》2010,12(1):R23