全文获取类型
收费全文 | 6545篇 |
免费 | 406篇 |
国内免费 | 1篇 |
专业分类
6952篇 |
出版年
2023年 | 28篇 |
2022年 | 63篇 |
2021年 | 92篇 |
2020年 | 79篇 |
2019年 | 84篇 |
2018年 | 131篇 |
2017年 | 104篇 |
2016年 | 184篇 |
2015年 | 267篇 |
2014年 | 358篇 |
2013年 | 495篇 |
2012年 | 570篇 |
2011年 | 504篇 |
2010年 | 340篇 |
2009年 | 283篇 |
2008年 | 429篇 |
2007年 | 371篇 |
2006年 | 369篇 |
2005年 | 326篇 |
2004年 | 336篇 |
2003年 | 340篇 |
2002年 | 313篇 |
2001年 | 65篇 |
2000年 | 62篇 |
1999年 | 62篇 |
1998年 | 64篇 |
1997年 | 59篇 |
1996年 | 58篇 |
1995年 | 47篇 |
1994年 | 60篇 |
1993年 | 42篇 |
1992年 | 40篇 |
1991年 | 31篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 16篇 |
1986年 | 11篇 |
1985年 | 16篇 |
1984年 | 16篇 |
1983年 | 22篇 |
1982年 | 15篇 |
1981年 | 27篇 |
1980年 | 21篇 |
1979年 | 14篇 |
1978年 | 6篇 |
1977年 | 17篇 |
1976年 | 7篇 |
1975年 | 7篇 |
1974年 | 9篇 |
排序方式: 共有6952条查询结果,搜索用时 15 毫秒
991.
992.
993.
994.
995.
Chiara Beltramo Nadia Valentini Ezio Portis Daniela Torello Marinoni Paolo Boccacci Maria Angelica Sandoval Prando Roberto Botta 《Molecular breeding : new strategies in plant improvement》2016,36(3):27
The European hazelnut (Corylus avellana L.) is the most economically important nut species in the Betulaceae family. Despite the need for new improved hazelnut cultivars, few breeding programs are carried out because of the large plant size, the long lifecycle of the plant, and the expense and time required. To date, there are no reports of maps with quantitative trait loci (QTL) in hazelnut. Our objective in the present study was to identify QTL associated with vegetative traits to allow marker-assisted selection (MAS). An F1 progeny (275 plants) of Tonda Gentile delle Langhe × Merveille de Bollwiller obtained in 2009 was used to develop a QTL linkage map for vigour, sucker habit, and time of bud burst, after three years of observations. A set of 163 plants were analysed with 152 microsatellite markers. A map of 11 linkage groups was obtained, covering 663.1 cM, and 15 QTLs were identified and mapped for the traits examined. Of them, 10 were ‘major’ QTL, including a stably expressed region on LG_02 for leaf bud burst. At least one major QTL for each year underlies the variation in each trait and a clustering of QTL for trunk circumference and suckers/trunk circumference ratio with high inter-trait correlations was observed on LG_05, suggesting a single pleiotropic locus. This research represents an initial step in the future identification of chromosomal regions carrying genes of interest, important for breeding programs and MAS. 相似文献
996.
Synergistic inhibition of pancreatic adenocarcinoma cell growth by trichostatin A and gemcitabine 总被引:1,自引:0,他引:1
Donadelli M Costanzo C Beghelli S Scupoli MT Dandrea M Bonora A Piacentini P Budillon A Caraglia M Scarpa A Palmieri M 《Biochimica et biophysica acta》2007,1773(7):1095-1106
We investigated the ability of the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) to interact with gemcitabine (GEM) in inducing pancreatic cancer cell death. The combined treatment with TSA and GEM synergistically inhibited growth of four pancreatic adenocarcinoma cell lines and induced apoptosis. This effect was associated with the induction of reactive oxygen species (ROS) by GEM, increased expression of the pro-apoptotic BIM gene by both TSA and GEM and downregulation of the 5'-nucleotidase UMPH type II gene by TSA. The expression of other genes critical for GEM resistance (nucleoside transporters, deoxycytidine kinase, cytidine deaminase, and ribonucleotide reductase genes) was not affected by TSA. The functional role of ROS in cell growth inhibition by GEM was supported by (i) a significantly reduced GEM-associated growth inhibition by the free radical scavenger N-acetyl-L-cysteine, and (ii) a positive correlation between the basal level of ROS and sensitivity to GEM in 10 pancreatic cancer cell lines. The functional role of both Bim and 5'-nucleotidase UMPH type II in cell growth inhibition by TSA and GEM was assessed by RNA interference assays. In vivo studies on xenografts of pancreatic adenocarcinoma cells in nude mice showed that the association of TSA and GEM reduced to 50% the tumour mass and did not cause any apparent form of toxicity, while treatments with TSA or GEM alone were ineffective. In conclusion, the present study demonstrates a potent anti-tumour activity of TSA/GEM combination against pancreatic cancer cells in vitro and in vivo, strongly supporting the use of GEM in combination with an HDAC inhibitor for pancreatic cancer therapy. 相似文献
997.
Paoli P Modesti A Magherini F Gamberi T Caselli A Manao G Raugei G Camici G Ramponi G 《Biochimica et biophysica acta》2007,1770(5):753-762
We mutated Trp(134) and Tyr(135) of the yeast LMW-PTP to explore their catalytic roles, demonstrating that the mutations of Trp(134) to Tyr or Ala, and Tyr(135) to Ala, all interfere with the formation of the phosphorylenzyme intermediate, a phenomenon that can be seen by the decrease in the kinetic constant of the chemical step (k(3)). Furthermore, we noted that the Trp(134) to Ala mutation causes a dramatic drop in k(cat)/K(m) and a slight enhancement of the dissociation constant K(s). The conservative mutant W134Y shows a k(cat)/K(m) very close to that of wild type, probably compensating the two-fold decrease of k(3) with an increase in substrate affinity. The Y135A mutation enhances the substrate affinity, but reduces the enzyme phosphorylation rate. The replacement of Trp(134) with alanine interferes with the partition between phosphorylenzyme hydrolysis and phosphotransfer from the phosphorylenzyme to glycerol and abolish the enzyme activation by adenine. Finally, we found that mutation of Trp(134) to Ala causes a dramatic change in the pH-rate profile that becomes similar to that of the D132A mutant, suggesting that an aromatic residue in position 134 is necessary to assist the proper positioning of the proton donor in the transition state of the chemical step. 相似文献
998.
Fabio Di Lisa Valeria Petronilli Raffaele Colonna Paolo Bernardi 《Biophysical journal》1999,77(3):1749-1750
999.
Claudia Galoppini Riccardo Patacchini Stefania Meini Stefania Viganò Mariella Tancredi Laura Quartara Antonio Triolo Carlo A. Maggi Paolo Rovero 《Letters in Peptide Science》1999,6(2-3):123-127
It has recently been shown that the biological activity of the second generation kinin B1 receptor selective antagonist, desArg10 HOE 140, can be improved by specific amino acid substitutions. Starting from this observation, we undertook a systematic structure-activity relationship study of this antagonist, based on the alanine-scan technique, in order to obtain useful information for the rational design of more analogues. Our data indicate that the sequence of desArg10 HOE 140 does not tolerate the replacement by Ala of most of its residues, with the exception of Ser in position 7 and, to a lesser extent, D-Arg in position 1 and Hyp in position 4. The most critical residues appear to be Pro in position 3 and the C-terminal dipeptide DTic-Oic; Ala replacement at these positions resultes in a total loss of activity. Moreover, replacement by Ala of Gly in position 5 reverts the activity of desArg10 HOE 140 to that of an agonist. 相似文献
1000.
Rafael E. Ummus Janice Onuki Dieter Drnemann Marisa H. G. Medeiros Paolo Di Mascio 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,729(1-2)
In this work we describe a sensitive method for the detection of 4,5-dioxovaleric acid (DOVA). 4,5-Dioxovaleric acid is derivatized with 2,3-diaminonaphthalene to form 3-(benzoquinoxalinyl-2)propionic acid (BZQ), a product with favorable UV absorbance and fluorescence properties. The high-performance liquid chromatographic method with UV absorbance and fluorescence detection is simple and its detection limit is approximately 100 fmol. This method was used to detect 4,5-dioxovaleric acid formation during metal-catalyzed 5-aminolevulinic acid (ALA) oxidation. Iron and ferritin were active in the formation of 4,5-dioxovaleric acid in the presence of 5-aminolevulinic acid. In addition, HPLC–MS–MS assay was used to characterize BZQ. The determination of 4,5-dioxovaleric acid is of great interest for the study of the mechanism of the metal-catalyzed damage of biomolecules by 5-aminolevulinic acid. This reaction may play a role in carcinogenesis after lead intoxication. The high frequency of liver cancer in acute intermittent porphyria patients may also be due to this reaction. 相似文献