全文获取类型
收费全文 | 808篇 |
免费 | 74篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 5篇 |
2021年 | 17篇 |
2020年 | 8篇 |
2019年 | 15篇 |
2018年 | 8篇 |
2017年 | 16篇 |
2016年 | 24篇 |
2015年 | 43篇 |
2014年 | 27篇 |
2013年 | 52篇 |
2012年 | 50篇 |
2011年 | 43篇 |
2010年 | 24篇 |
2009年 | 31篇 |
2008年 | 32篇 |
2007年 | 29篇 |
2006年 | 34篇 |
2005年 | 35篇 |
2004年 | 33篇 |
2003年 | 31篇 |
2002年 | 36篇 |
2001年 | 26篇 |
2000年 | 24篇 |
1999年 | 21篇 |
1998年 | 14篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1993年 | 8篇 |
1992年 | 9篇 |
1991年 | 9篇 |
1990年 | 16篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 5篇 |
1985年 | 9篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1971年 | 3篇 |
1969年 | 3篇 |
排序方式: 共有883条查询结果,搜索用时 15 毫秒
61.
Increased physical exercise is known to prevent leg problems in meat-type chickens. Our aims were to study in detail the organisation of general and locomotor activity, to determine how physical exercise could be promoted and to investigate the effects of tonic immobility (TI) duration on spontaneous activity. Chicks were allocated to two groups according to their TI duration at 3 and 20 days (fearful birds, HF, n=11; non-fearful birds, LF, n=14). The behaviour patterns expressed by awake birds were recorded as 'activity bouts'. Activity bouts were then classified into five classes according to the most long-lasting activity in the bout. The behaviour patterns were similar in both groups. The FORAGING class contained long-lasting bouts with high levels of locomotor activity which decreased considerably with age, when bouts of EATING and DRINKING classes became more and more numerous. Bouts in the PREENING and NONE classes contained low activity. In conclusion, the level of activity in home pens was poorly related to TI. Categorisation of bouts into five classes is valuable to understand the general organisation of activity in chickens. The FORAGING class included bouts with high levels of locomotion and it could thus be used as a general indicator of activity. 相似文献
62.
63.
von Samson-Himmelstjerna G Pape M von Witzendorff C Schnieder T 《The Journal of parasitology》2002,88(2):254-257
It has been shown that benzimidazole (BZ) resistance in sheep gastrointestinal nematodes is linked with an increase in beta-tubulin codon 200 tyrosine-expressing alleles in the resistant parasite populations. Here, an allele-specific PCR has been developed for the discrimination of the TAC/TTC polymorphism in the beta-tubulin 200 codon of small strongyles. One reverse primer was used in 2 separate amplifications with 1 of 2 forward primers that differed only in their final 3' nucleotide. The primers flank a facultative intron/exon. Therefore, the amplified fragments are either 251 or 308 bp in size, depending on the presence or absence of the intron in individual worms. Amplification of genomic DNA isolated from single adult small strongyles from a set of 7 species consistently generated allele-specific products. Three worms each of the following species were used: Cylicocyclus nassatus, Cylicocyclus insigne, Cylicocyclus elongatus, Cylicocyclus radiatus, Cyathostomum pateratum, Cyathostomum catinatum, and Cyathostomum coronatum. PCR with DNA isolated from single larvae also reproducibly generated specific fragments. This method might be applied for the future assessment of allele frequencies in susceptible and resistant populations to further investigate the mechanism of BZ-resistance in small strongyles. 相似文献
64.
Marchand P Le Borgne M Na YM Pagniez F Abdala H Le Baut G Le Pape P 《Journal of enzyme inhibition and medicinal chemistry》2002,17(6):353-358
The goal of the present study was to evaluate several azolyl-substituted indoles as new antileishmanial agents. Ten 3-(alpha-azolylbenzyl)indoles have been synthesized using Friedel-Crafts acylation as a key-step. All the target compounds were found to display high levels of activity when tested against Leishmania mexicana promastigotes in vitro. The most active compounds, showing an IC50 < 1 microM, were 5-bromo-1-ethyl-3-[(2,4-dichlorophenyl)(1H-imidazol-1-yl)methyl]-1H-indole 15 and its triazole analogue 17. Four representative compounds 15, 17, 22 and, 23 were also tested against intracellular amastigotes of L. mexicana using ketoconazole and meglumine antimoniate as reference compounds, the results of which are discussed. 相似文献
65.
66.
Hanselman JC Vartanian MA Koester BP Gray SA Essenburg AD Rea TJ Bisgaier CL Pape ME 《Molecular and cellular biochemistry》2001,217(1-2):91-97
Two alternatively spliced forms of human PPAR mRNA, PPAR1 and PPAR2, have been identified. PPAR1 mRNA gives rise to an active PPAR protein while PPAR2 mRNA gives rise to a form of PPAR which lacks the ligand-binding domain. PPAR2 is unable to activate a peroxisome proliferator response element (PPRE) reporter gene construct in transient transfection assays. Both PPAR1 and PPAR2 mRNA are present in human liver, kidney, testes, heart, small intestine, and smooth muscle. In human liver, PPAR2 mRNA abundance is approximately half that of PPAR1 mRNA; a correlation analysis of PPAR1 and PPAR2 mRNA mass revealed an r-value of 0.75 (n = 18). Additional studies with intact liver from various species, showed that the PPAR2/PPAR1 mRNA ratios in rat, rabbit, and mouse liver were less than 0.10; significantly lower than the 0.3 and 0.5 ratios observed in monkey and human livers, respectively. To determine if a high PPAR2/PPAR1 mRNA ratio was associated with insensitivity to peroxisome proliferators, we treated human, rat, and rabbit hepatocytes with WY14643, a potent PPARa activator, and measured acyl CoA oxidase (ACO) mRNA levels. Rat ACO mRNA levels increased markedly in response to WY14643 while human and rabbit hepatocytes were unresponsive. Thus, although the PPAR2/PPAR1 mRNA ratio is low in rabbits, this species is not responsive to peroxisome proliferators. Further studies with male and female rats, which vary significantly in their response to peroxisome proliferators, showed little difference in the ratio of PPAR2/PPAR1 mRNA. These data suggest that selective PPAR2 mRNA expression is not the basis for differential species or gender responses to peroxisome proliferators. 相似文献
67.
Vigorous peripheral blood cytotoxic T cell response during the acute phase of hepatitis C virus infection 总被引:7,自引:0,他引:7
Cucchiarini M Kammer AR Grabscheid B Diepolder HM Gerlach TJ Grüner N Santantonio T Reichen J Pape GR Cerny A 《Cellular immunology》2000,203(2):111-123
After infection by hepatitis C virus (HCV), a minority of patients develop acute symptomatic disease and some of them are able to clear the virus. In this study, we analyzed peripheral blood mononuclear cells from nine patients with acute symptomatic disease with respect to their cytotoxic T lymphocyte (CTL) response using a panel of HCV-derived peptides in a semiquantitative secondary in vitro culture system. We could detect early CTL responses in 67% of these patients. The CTL responses were directed against multiple viral epitopes, in particular within the structural (core 2-9, core 35-44, core 131-140, and core 178-187) and nonstructural regions of the virus (NS3 1073-1081, NS3 1406-1415, NS4 1807-1816, NS5 2252-2260, and NS5B 2794-2802). We compared the CTL responses displayed by recently and chronically infected HLA-A2-positive patients. Virus-specific CTLs were detectable in chronic carriers but the percentage of positive peptide-specific CTL responses was significantly higher in recently infected patients (P = 0.002). Follow-up of recently infected patients during subsequent disease development showed a significant decrease in the values and proportions of positive peptide-specific CTL responses (P = 0.002 and 0.013, respectively). Patients with limited viral replication exhibited significantly more vigorous early responses (P = 0.024). These data suggest a protective role for the early antiviral CTL response in HCV infection. 相似文献
68.
Dedicated Roles of Plastid Transketolases during the Early Onset
of Isoprenoid Biogenesis in Pepper Fruits 总被引:15,自引:1,他引:14
下载免费PDF全文
![点击此处可从《Plant physiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Florence Bouvier Alain d''Harlingue Claude Suire Ralph A. Backhaus Bilal Camara 《Plant physiology》1998,117(4):1423-1431
Isopentenyl diphosphate (IPP), which is produced from mevalonic acid or other nonmevalonic substrates, is the universal precursor of isoprenoids in nature. Despite the presence of several isoprenoid compounds in plastids, enzymes of the mevalonate pathway leading to IPP formation have never been isolated or identified to our knowledge. We now describe the characterization of two pepper (Capsicum annuum L.) cDNAs, CapTKT1 and CapTKT2, that encode transketolases having distinct and dedicated specificities. CapTKT1 is primarily involved in plastidial pentose phosphate and glycolytic cycle integration, whereas CapTKT2 initiates the synthesis of isoprenoids in plastids via the nonmevalonic acid pathway. From pyruvate and glyceraldehyde-3-phosphate, CapTKT2 catalyzes the formation of 1-deoxy-xylulose-5-phosphate, the IPP precursor. CapTKT1 is almost constitutively expressed during the chloroplast-to-chromoplast transition, whereas CapTKT2 is overexpressed during this period, probably to furnish the IPP necessary for increased carotenoid biosynthesis. Because deoxy-xylulose phosphate is shared by the plastid pathways of isoprenoid, thiamine (vitamin B1), and pyridoxine (vitamin B6) biosynthesis, our results may explain why albino phenotypes usually occur in thiamine-deficient plants. 相似文献
69.
Andreas Jodal Fabienne Pape Christoph Becker-Pauly Ole Maas Roger Schibli Martin Béhé 《PloS one》2015,10(4)
Background
Cleavable linkers, which are specifically cleaved by defined conditions or enzymes, are powerful tools that can be used for various purposes. Amongst other things, they have been successfully used to deliver toxic payloads as prodrugs into target tissues. In this work novel linker sequences targeting meprin β, a metalloprotease expressed in the kidney brush-border membrane, were designed and included in the sequence of three radiolabelled exendin-4 derivatives. As radiolabelled exendin-4 derivatives strongly accumulate in the kidneys, we hypothesised that specific cleavage of the radiolabelled moiety at the kidney brush-border membrane would allow easier excretion of the activity into the urine and therefore improve the pharmacological properties of the peptide.Results
The insertion of a cleavable linker did not negatively influence the in vitro properties of the peptides. They showed a good affinity to the GLP-1 receptor expressed in CHL cells, a high internalisation and sufficiently high stability in fresh human blood plasma. In vitro digestion with recombinant meprin β rapidly metabolised the corresponding linker sequences. After 60 min the majority of the corresponding peptides were digested and at the same time the anticipated fragments were formed. The peptides were also quickly metabolised in CD1 nu/nu mouse kidney homogenates. Immunofluorescence staining of meprin β in kidney sections confirmed the expression of the protease in the kidney brush-border membrane. Biodistribution in GLP-1 receptor positive tumour-xenograft bearing mice revealed high specific uptake of the 111In-labelled tracers in receptor positive tissue. Accumulation in the kidneys, however, was still high and comparable to the lead compound 111In-Ex4NOD40.Conclusion
In conclusion, we show that the concept of cleavable linkers specific for meprin β is feasible, as the peptides are rapidly cleaved by the enzyme while retaining their biological properties. 相似文献70.
Joan?M.?BernhardEmail authorView authors OrcID profile Colin?R.?Morrison Ellen?Pape David?J.?Beaudoin M.?Antonio?Todaro Maria?G.?Pachiadaki Konstantinos?Ar.?Kormas Virginia?P.?Edgcomb 《BMC biology》2015,13(1):105