全文获取类型
收费全文 | 1535篇 |
免费 | 155篇 |
出版年
2022年 | 9篇 |
2021年 | 20篇 |
2020年 | 10篇 |
2019年 | 18篇 |
2018年 | 18篇 |
2017年 | 20篇 |
2016年 | 28篇 |
2015年 | 38篇 |
2014年 | 57篇 |
2013年 | 67篇 |
2012年 | 65篇 |
2011年 | 82篇 |
2010年 | 32篇 |
2009年 | 42篇 |
2008年 | 58篇 |
2007年 | 58篇 |
2006年 | 51篇 |
2005年 | 61篇 |
2004年 | 41篇 |
2003年 | 45篇 |
2002年 | 29篇 |
2001年 | 54篇 |
2000年 | 44篇 |
1999年 | 51篇 |
1998年 | 31篇 |
1997年 | 21篇 |
1996年 | 21篇 |
1995年 | 22篇 |
1994年 | 29篇 |
1993年 | 18篇 |
1992年 | 33篇 |
1991年 | 30篇 |
1990年 | 26篇 |
1989年 | 34篇 |
1988年 | 23篇 |
1987年 | 32篇 |
1986年 | 25篇 |
1985年 | 27篇 |
1984年 | 23篇 |
1983年 | 23篇 |
1982年 | 15篇 |
1981年 | 16篇 |
1980年 | 20篇 |
1979年 | 11篇 |
1978年 | 14篇 |
1977年 | 10篇 |
1976年 | 21篇 |
1973年 | 12篇 |
1972年 | 9篇 |
1971年 | 9篇 |
排序方式: 共有1690条查询结果,搜索用时 31 毫秒
111.
Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors 总被引:4,自引:0,他引:4
Han Y Giroux A Grimm EL Aspiotis R Francoeur S Bayly CI Mckay DJ Roy S Xanthoudakis S Vaillancourt JP Rasper DM Tam J Tawa P Thornberry NA Paterson EP Garcia-Calvo M Becker JW Rotonda J Nicholson DW Zamboni RJ 《Bioorganic & medicinal chemistry letters》2004,14(3):805-808
The discovery of a series of potent, selective and reversible dipeptidyl caspase-3 inhibitors are reported. The iterative discovery process of using combinatorial chemistry, parallel synthesis, moleculare modelling and structural biology will be discussed. 相似文献
112.
Biosensor reporting of root exudation from Hordeum vulgare in relation to shoot nitrate concentration 总被引:4,自引:0,他引:4
The aim of this study was to determine the relationship between shoot nitrate concentration, mediated by nitrate supply to roots, and root exudation from Hordeum vulgare. Plants were grown for 14 d in C-free sand microcosms, supplied with nutrient solution containing 2 mM nitrate. After this period, three treatments were applied for a further 14 d: (A) continued supply with 2 mM nitrate (zero boost), (B) supply with 10 mM nitrate (low boost), and (C) supply with 20 mM nitrate (high boost). At the end of the treatment period, a bacterial biosensor (Pseudomonas fluorescens 10586 pUCD607, marked with the lux CDABE genes for bioluminescence) was applied to the microcosms to report on C-substrate availability, as a consequence of root exudation. The nitrate boost treatments significantly affected shoot nitrate concentrations, in the order C>B>A. In treatments receiving a nitrate boost (B, C), increased shoot nitrate concentration was correlated with increased plant biomass, reduced root length, reduced number of root tips, and increased mean root diameter, relative to the no boost treatment (A). Imaging of biosensor bioluminescence (proportional to metabolic activity in response to availability of root exudates) indicated that root exudation increased with decreasing shoot nitrate concentration. Biosensor reporting of root C-flow indicated that exudation was greater from root tip regions than from the whole root, but that specific exudation rates for all sites were unaffected by treatments. Total root exudation across treatments was found to be closely correlated with total root length, indicating that increased root exudation, per unit root biomass, with decreasing nitrate supply was associated with altered root morphology, as a consequence of systemic plant responses to internal N-status. 相似文献
113.
Wells RW Morris GP Blennerhassett MG Paterson WG 《Canadian journal of physiology and pharmacology》2003,81(5):451-458
Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue. 相似文献
114.
Roh M Paterson AJ Asa SL Chin E Kudlow JE 《Molecular endocrinology (Baltimore, Md.)》2001,15(4):600-613
The epidermal growth factor receptor (EGFR) and its ligands EGF and transforming growth factor-alpha (TGF alpha) are expressed in the anterior pituitary, and overexpression of TGF alpha in the lactotrope cells of the pituitary gland in transgenic mice results in lactotrope hyperplasia and adenomata, suggesting a role for EGFR signaling in pituitary cell proliferation. To address the role of EGFR signaling in pituitary development in vivo, we blocked EGFR signaling in transgenic mice using the dominant negative properties of a mutant EGFR lacking an intracellular protein kinase domain (EGFR-tr). We directed EGFR-tr expression to GH- and PRL- producing cells using GH and PRL promoters, and a tetracycline-inducible gene expression system, to allow temporal control of gene expression. EGFR-tr overexpression in GH-producing cells during embryogenesis resulted in dwarf mice with pituitary hypoplasia. Both somatotrope and lactotrope development were blocked. However, when EGFR-tr overexpression was delayed to the postnatal period either by directing its expression with the PRL promoter or by delaying the onset of induction with tetracycline in the GH cells, no specific phenotype was observed. Lactotrope hyperplasia during pregnancy also occurred normally in the PRL-EGFR-tr mice. These data suggest that EGFR signaling is required for the differentiation and/or maintenance of somatomammotropes early in pituitary organogenesis but not later in life. (Molecular Endocrinology 15: 600-613, 2001) 相似文献
115.
Crossman A Paterson MJ Ferguson MA Smith TK Brimacombe JS 《Carbohydrate research》2002,337(21-23):2049-2059
1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-1-O-hexadecyl-myo-inositol (14), 1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(octadecyl phosphate) (18), 1-D-6-O-(2-amino-2-deoxy-beta-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (24), 1-D-6-O-(2-amino-2-deoxy-alpha-D-mannopyranosyl)-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (30) and the corresponding 2-amino-2-deoxy-alpha-D-galactopyranosyl analogue 36 have been prepared and tested in cell-free assays as substrate analogues/inhibitors of alpha-(1 --> 4)-D-mannosyltransferases that are active early on in the glycosylphosphatidylinositol (GPI) biosynthetic pathways of Trypanosoma brucei and HeLa (human) cells. The corresponding N-acetyl derivatives of these compounds were similarly tested as candidate substrate analogues/inhibitors of the N-deacetylases present in both systems. Following on from an early study, 1-L-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-methyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (44) was prepared and tested as an inhibitor of the trypanosomal alpha-(1 --> 4)-D-mannosyltransferase. A brief summary of the biological evaluation of the various analogues is provided. 相似文献
116.
Schloss J Mitchell E White M Kukatla R Bowers E Paterson H Kresovich S 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,105(6-7):912-920
In this study, we collected and analyzed DNA sequence data for 789 previously mapped RFLP probes from Sorghum bicolor (L.) Moench. DNA sequences, comprising 894 non-redundant contigs and end sequences, were searched against three GenBank databases, nucleotide (nt), protein (nr) and EST (dbEST), using BLAST algorithms. Matching ESTs were also searched against nt and nr. Translated DNA sequences were then searched against the conserved domain database (CDD) to determine if functional domains/motifs were congruent with the proteins identified in previous searches. More than half (500/894 or 56%) of the query sequences had significant matches in at least one of the GenBank searches. Overall, proteins identified for 148 sequences (17%) were consistent among all searches, of which 66 sequences (7%) contained congruent coding domains. The RFLP probe sequences were also evaluated for the presence of simple sequence repeats (SSRs) and 60 SSRs were developed and assayed in an array of sorghum germplasm comprising inbreds, landraces and wild relatives. Overall, these SSR loci had lower levels of polymorphism ( D = 0.46, averaged over 51 polymorphic loci) compared with sorghum SSRs that were isolated by library hybridization screens ( D = 0.69, averaged over 38 polymorphic loci). This result was probably due to the relatively small proportion of di-nucleotide repeat-containing markers (42% of the total SSR loci) obtained from the DNA sequence data. These di-nucleotide markers also contained shorter repeat motifs than those isolated from genomic libraries. Based on BLAST results, 24 SSRs (40%) were located within, or near, previously annotated or hypothetical genes. We determined the location of 19 of these SSRs relative to putative coding regions. In general, SSRs located in coding regions were less polymorphic ( D = 0.07, averaged over three loci) than those from gene flanking regions, UTRs and introns ( D = 0.49, averaged over 16 loci). The sequence information and SSR loci generated through this study will be valuable for application to sorghum genetics and improvement, including gene discovery, marker-assisted selection, diversity and pedigree analyses, comparative mapping and evolutionary genetic studies. 相似文献
117.
Mapping QTLs for field resistance to the rice blast pathogen and evaluating their individual and combined utility in improved varieties 总被引:2,自引:0,他引:2
Tabien E Li Z Paterson H Marchetti A Stansel W Pinson M 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,105(2-3):313-324
Lines from a Lemont x Teqing recombinant inbred population were evaluated for dilatory resistance to rice blast disease using: (1) the Standard Evaluation System (SES) for rating leaf blast, (2) the percentage diseased leaf area (%DLA), and (3) the area under a disease progress curve (AUDPC). RFLP mapping using 175 well-distributed loci revealed nine QTLs, one each on chromosomes 1, 2, 3, 4, 6, 7 and 9, with two loci on chromosome 12. All nine putative QTLs were associated with AUDPC, six with both a %DLA and a SES rating. Teqing contributed the resistance allele for all these loci except for the one located on chromosome 4. Individual QTLs accounted for 5-32% of the observed phenotypic variation, and combined QTL models accounted for 43-53%. Three QTLs were located near three of the four major resistance genes previously identified in this population. The resistances of both Lemont and Teqing were attributable to a combination of both major genes capable of inducing hypersensitive reactions and minor genes causing less-distinctive phenotypic differences. Interactions were noted between QTLs and major genes. Our findings are in support of the strategy of pyramiding major genes and QTLs in carefully selected combinations to develop improved varieties with resistance to the blast fungus that is both broad in spectrum and durable. 相似文献
118.
Smith TK Gerold P Crossman A Paterson MJ Borissow CN Brimacombe JS Ferguson MA Schwarz RT 《Biochemistry》2002,41(41):12395-12406
The substrate specificities of the early glycosylphosphatidylinositol biosynthetic enzymes of Plasmodium were determined using substrate analogues of D-GlcN(alpha)1-6-D-myo-inositol-1-HPO(4)-sn-1,2-dipalmitoylglycerol (GlcN-PI). Similarities between the Plasmodium and mammalian (HeLa) enzymes were observed. These are as follows: (i) The presence and orientation of the 2'-acetamido/amino and 3'-OH groups are essential for substrate recognition for the de-N-acetylase, inositol acyltransferase, and first mannosyltransferase enzymes. (ii) The 6'-OH group of the GlcN is dispensable for the de-N-acetylase, inositol acyltransferase, all four of the mannosyltransferases, and the ethanolamine phosphate transferase. (iii) The 4'-OH group of GlcNAc is not required for recognition, but substitution interferes with binding to the de-N-acetylase. The 4'-OH group of GlcN is essential for the inositol acyltransferase and first mannosyltransferase. (iv) The carbonyl group of the natural 2-O-hexadecanyl ester of GlcN-(acyl)PI is essential for substrate recognition by the first mannosyltransferase. However, several differences were also discovered: (i) Plasmodium-specific inhibition of the inositol acyltransferase was detected with GlcN-[L]-PI, while GlcN-(2-O-alkyl)PI weakly inhibited the first mannosyltransferase in a competitive manner. (ii) The Plasmodium de-N-acetylase can act on analogues containing N-benzoyl, GalNAc, or betaGlcNAc whereas the human enzyme cannot. Using the parasite specificity of the later two analogues with the known nonspecific de-N-acetylase suicide inhibitor [Smith, T. K., et al. (2001) EMBO J. 20, 3322-3332], GalNCONH(2)-PI and GlcNCONH(2)-beta-PI were designed and found to be potent (IC(50) approximately 0.2 microM), Plasmodium-specific suicide substrate inhibitors. These inhibitors could be potential lead compounds for the development of antimalaria drugs. 相似文献
119.
Mapping of genes controlling aluminum tolerance in rice: comparison of different genetic backgrounds 总被引:8,自引:0,他引:8
Nguyen VT Nguyen BD Sarkarung S Martinez C Paterson AH Nguyen HT 《Molecular genetics and genomics : MGG》2002,267(6):772-780
Aluminum toxicity is the main factor limiting the productivity of crop plants in acid soils, particularly in the tropics and subtropics. In this study, a doubled-haploid population derived from the rice ( Oryza sativa L.) breeding lines CT9993 and IR62266 was used to map genes controlling Al tolerance. A genetic linkage map consisting of 280 DNA markers (RFLP, AFLP and SSR) was constructed to determine the position and nature of quantitative trait loci (QTLs) affecting Al tolerance. Three characters - control root length (CRL), Al-stressed root length (SRL) and root length ratio (RR) - were evaluated for the DH lines and the parents at the seedling stage in nutrient solution. A total of 20 QTLs controlling root growth under Al stress and control conditions were detected and distributed over 10 of the 12 rice chromosomes, reflecting multigenic control of these traits. The two QTLs of largest effect, qALRR-1-1 and qALRR-8 for root length ratio (a measurement of Al tolerance) were localized on chromosomes 1 and 8, respectively. Three other QTLs in addition to qALRR-8 were apparently unique in the CT9993 x IR62266 mapping population, which may explain the high level of Al tolerance in CT9993. Comparative mapping identified a conserved genomic region on chromosome 1 associated with Al tolerance across three rice genetic backgrounds. This region provides an important starting point for isolating genes responsible for different mechanisms of aluminum tolerance and understanding the genetic nature of this trait in rice and other cereals. 相似文献
120.
QTL analysis of genotype × environment interactions affecting cotton fiber quality 总被引:13,自引:0,他引:13
Paterson AH Saranga Y Menz M Jiang CX Wright RJ 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2003,106(3):384-396
Cotton is unusual among major crops in that large acreages are grown under both irrigated and rainfed conditions, making genotype x environment interactions of even greater importance than usual in designing crop-improvement strategies. We describe the impact of well-watered versus water-limited growth conditions on the genetic control of fiber quality, a complex suite of traits that collectively determine the utility of cotton. Fiber length, length uniformity, elongation, strength, fineness, and color (yellowness) were influenced by 6, 7, 9, 21, 25 and 11 QTLs (respectively) that could be detected in one or more treatments. The genetic control of cotton fiber quality was markedly affected both by general differences between growing seasons ("years") and by specific differences in water management regimes. Seventeen QTLs were detected only in the water-limited treatment while only two were specific to the well-watered treatment, suggesting that improvement of fiber quality under water stress may be even more complicated than improvement of this already complex trait under well-watered conditions. In crops such as cotton with widespread use of both irrigated and rainfed production systems, the need to manipulate larger numbers of genes to confer adequate quality under both sets of conditions will reduce the expected rate of genetic gain. These difficulties may be partly ameliorated by efficiencies gained through identification and use of diagnostic DNA markers, including those identified herein. 相似文献