全文获取类型
收费全文 | 7496篇 |
免费 | 706篇 |
国内免费 | 2篇 |
专业分类
8204篇 |
出版年
2023年 | 36篇 |
2022年 | 57篇 |
2021年 | 119篇 |
2020年 | 91篇 |
2019年 | 85篇 |
2018年 | 122篇 |
2017年 | 128篇 |
2016年 | 198篇 |
2015年 | 315篇 |
2014年 | 287篇 |
2013年 | 395篇 |
2012年 | 499篇 |
2011年 | 507篇 |
2010年 | 325篇 |
2009年 | 309篇 |
2008年 | 418篇 |
2007年 | 400篇 |
2006年 | 397篇 |
2005年 | 376篇 |
2004年 | 362篇 |
2003年 | 322篇 |
2002年 | 310篇 |
2001年 | 186篇 |
2000年 | 184篇 |
1999年 | 180篇 |
1998年 | 93篇 |
1997年 | 76篇 |
1996年 | 74篇 |
1995年 | 83篇 |
1994年 | 62篇 |
1993年 | 41篇 |
1992年 | 107篇 |
1991年 | 103篇 |
1990年 | 98篇 |
1989年 | 62篇 |
1988年 | 73篇 |
1987年 | 74篇 |
1986年 | 68篇 |
1985年 | 50篇 |
1984年 | 40篇 |
1983年 | 36篇 |
1982年 | 33篇 |
1981年 | 44篇 |
1979年 | 33篇 |
1978年 | 26篇 |
1977年 | 26篇 |
1976年 | 23篇 |
1975年 | 25篇 |
1973年 | 30篇 |
1971年 | 39篇 |
排序方式: 共有8204条查询结果,搜索用时 15 毫秒
71.
C. de la Chevrotière S. C. Bishop R. Arquet J. C. Bambou L. Schibler Y. Amigues C. Moreno N. Mandonnet 《Animal genetics》2012,43(6):768-775
This study aimed to identify regions of the genome affecting resistance to gastrointestinal nematodes in a Creole goat population naturally exposed to a mixed nematode infection (Haemonchus contortus, Trichostrongylus colubriformis and Oesophagostomum columbianum) by grazing on irrigated pasture. A genome‐wide quantitative trait loci (QTL) scan was performed on 383 offspring from 12 half‐sib families. A total of 101 microsatellite markers were genotyped. Traits analysed were faecal egg count (FEC), packed cell volume (PCV), eosinophil count and bodyweight (BW) at 7 and 11 months of age. Levels of activity of immunoglobulin A (IgA) and activity of immunoglobulin E (IgE) anti‐Haemonchus contortus L3 crude extracts and adult excretion/secretion products (ESPs) were also analysed. Using interval mapping, this study identified 13 QTL for parasite resistance. Two QTL linked with FEC were found on chromosomes 22 and 26. Three QTL were detected on chromosomes 7, 8 and 14 for eosinophil counts. Three QTL linked with PCV were identified on chromosomes 5, 9 and 21. A QTL for BW at 7 months of age was found on chromosome 6. Lastly, two QTL detected on chromosomes 3 and 10 were associated with IgE anti‐L3, and IgE anti‐ESP was linked with two QTL on chromosomes 1 and 26. This study is the first to have identified regions of the genome linked with nematode resistance in a goat population using a genome scan. These results provide useful tools for the understanding of parasite resistance in small ruminants. 相似文献
72.
Pedro Casado Maria P Alcolea Francesco Iorio Juan-Carlos Rodríguez-Prados Bart Vanhaesebroeck Julio Saez-Rodriguez Simon Joel Pedro R Cutillas 《Genome biology》2013,14(4):R37
Background
Tumor classification based on their predicted responses to kinase inhibitors is a major goal for advancing targeted personalized therapies. Here, we used a phosphoproteomic approach to investigate biological heterogeneity across hematological cancer cell lines including acute myeloid leukemia, lymphoma, and multiple myeloma.Results
Mass spectrometry was used to quantify 2,000 phosphorylation sites across three acute myeloid leukemia, three lymphoma, and three multiple myeloma cell lines in six biological replicates. The intensities of the phosphorylation sites grouped these cancer cell lines according to their tumor type. In addition, a phosphoproteomic analysis of seven acute myeloid leukemia cell lines revealed a battery of phosphorylation sites whose combined intensities correlated with the growth-inhibitory responses to three kinase inhibitors with remarkable correlation coefficients and fold changes (> 100 between the most resistant and sensitive cells). Modeling based on regression analysis indicated that a subset of phosphorylation sites could be used to predict response to the tested drugs. Quantitative analysis of phosphorylation motifs indicated that resistant and sensitive cells differed in their patterns of kinase activities, but, interestingly, phosphorylations correlating with responses were not on members of the pathway being targeted; instead, these mainly were on parallel kinase pathways.Conclusion
This study reveals that the information on kinase activation encoded in phosphoproteomics data correlates remarkably well with the phenotypic responses of cancer cells to compounds that target kinase signaling and could be useful for the identification of novel markers of resistance or sensitivity to drugs that target the signaling network. 相似文献73.
Within 40 years of experimental studies in prebiotic chemistry, most of the building blocks of the living systems have been synthesized in plausible conditions of the primitive Earth. The starting ingredients correspond to two complementary classes: volatile organics, and their non volatile oligomers. They may have been formed in the atmosphere on the primitive Earth and/or imported by extra-terrestrial sources. Organic chemistry is involved in meteorites, comets, in the giant planets and several of their satellites. Again this chemistry presents the two complementary aspects. In particular, with a dense reduced atmosphere rich in organic compounds in gas and aerosol phases, Titan appears as a natural laboratory for studying prebiotic chemistry at a planetary scale. 相似文献
74.
Vikas SharmaJente Boonen Nagendra S. ChauhanMayank Thakur Bart De SpiegeleerV.K. Dixit 《Phytomedicine》2011,18(13):1161-1169
According to Indian Systems of Medicine, Spilanthes acmella (L.) Murr. (Family - Asteraceae), is considered effective in the treatment of sexual deficiencies especially due to ageing. In the present study, characterization of ethanolic extracts of the Spilanthes acmella flower and its effect on general mating pattern, penile erection and serum hormone levels of normal male Wistar albino rats were investigated and compared with sildenafil citrate. In vitro nitric oxide release was also investigated in human corpus cavernosum cell line. As N-alkylamides are a promising group, their profiling was performed using a gradient reversed phase high performance liquid chromatography/electrospray ionization ion trap mass spectrometry (HPLC/ESI-MS) method on an embedded polar column. MS1 and MS2 fragmentation data were used for identification purposes. For assessment of sexual behavior, animals were divided into five groups of eight male rats. The extracts (50, 100 and 150 mg/kg body weight/day) and sildenafil citrate (5 mg/kg body weight/day) (positive control) were administered orally for 28 days. The behavioral and sexual parameters were observed at days 0, 15, 28 and after a lapse of 7 and 14 days of discontinuance of drug treatment. Five N-isobutylamides, one 2-methylbutylamide and one 2-phenylethylamide were identified. The orally administered extract had a dose dependent positive effect on mounting frequency, intromission frequency and ejaculation frequency and the most significant effects (p < 0.05) were observed at 150 mg/kg treatment, even after a lapse of 7 and 14 days of discontinuance of drug treatment. A dose dependent effect was also observed on the FSH, LH and testosterone serum levels. With 150 mg/kg of ethanolic extract the values for FSH, LH and testosterone were 3.10 ± 0.25 mlU/ml, 6.87 ± 0.18 mlU/ml and 3.72 ± 0.12 ng/ml, respectively. In vitro nitric oxide release was 21.7 ± 2.9 μM, which was significantly higher compared to the control group (p < 0.01). Sildenafil citrate exhibited also a significant effect on NO release, but no effect on hormone levels of rats was observed. The aphrodisiac potential of an ethanolic Spilanthes acmella extract was demonstrated in vitro and in vivo. N-Alkylamides might attribute to the improved sexual potential. Study lends support to the traditional utilization of S. acmella as a sexual stimulating agent. 相似文献
75.
Galinier A Carrière A Fernandez Y Carpéné C André M Caspar-Bauguil S Thouvenot JP Périquet B Pénicaud L Casteilla L 《The Journal of biological chemistry》2006,281(18):12682-12687
The role of inflammation and oxidative stress in the development of obesity and associated metabolic disorders is under debate. We investigated the redox metabolism in a non-diabetic obesity model, i.e. 11-week-old obese Zucker rats. Antioxidant enzyme activities, lipophilic antioxidant (alpha-tocopherol, coenzymes Q) and hydrophilic antioxidant (glutathione, vitamin C) contents and their redox state (% oxidized form), were studied in inguinal white fat and compared with blood and liver. The adipose tissues of obese animals showed a specific higher content of hydrophilic molecules in a lower redox state than those of lean animals, which were associated with lower lipophilic molecule content and lipid peroxidation. Conversely and as expected, glutathione content decreased and its redox state increased in adipose tissues of rats subjected to lipopolysaccharide-induced systemic oxidative stress. In these in vivo models, oxidative stress and obesity thus had opposite effects on adipose tissue redox state. Moreover, the increase in glutathione content and the decrease of its redox state by antioxidant treatment promoted in vitro the accumulation of triglycerides in preadipocytes. Taken together and contrary to the emergent view, our results suggest that obesity is associated with an intracellular reduced redox state that promotes on its own the development of a deleterious proadipogenic process. 相似文献
76.
Effects of AY 9944 on low density lipoprotein metabolism in cultured human fibroblasts 总被引:1,自引:0,他引:1
J C Mazière C Mazière L Mora J Gardette C Wolf D Rainteau V Barbu C Roux J Polonovski 《Biochemical and biophysical research communications》1984,122(3):955-959
Treatment of cultured human fibroblasts with the hypocholesterolemic drug AY 9944 resulted in a marked increase in low density lipoprotein internalization and degradation for concentrations up to 5 X 10(-6)M. Low density lipoprotein binding was less affected. Concentrations above 5 X 10(-6)M resulted in a relative decrease in low density lipoprotein degradation, whereas binding and internalization plateaued. The stimulation of low density lipoprotein internalization took place within the first hours of incubation of cells with the drug, which suggests a direct effect on the cell membrane. Such phenomenon could account at least partially for the hypocholesterolemic effect of the drug, besides its inhibitory effect on 7-dehydrocholesterol reductase. 相似文献
77.
Identification and Differentiation of Legionella pneumophila and Legionella spp. with Real-Time PCR Targeting the 16S rRNA Gene and Species Identification by mip Sequencing 总被引:1,自引:0,他引:1 下载免费PDF全文
Fluorescent resonance energy transfer probes targeting the 16S rRNA gene were constructed for a sensitive and specific real-time PCR for identification and differentiation of Legionella pneumophila from other Legionella spp. For identification of non-L. pneumophila spp. by direct amplicon sequencing, two conventional PCR assays targeting the mip gene were established. 相似文献
78.
Pacchiarotta T Hensbergen PJ Wuhrer M van Nieuwkoop C Nevedomskaya E Derks RJ Schoenmaker B Koeleman CA van Dissel J Deelder AM Mayboroda OA 《Journal of Proteomics》2012,75(3):1067-1073
Urinary tract infection (UTI) is the most common bacterial infection leading to substantial morbidity and considerable health care expenditures across all ages. Here we present an exploratory UPLC-MS study of human urine in the context of febrile, complicated urinary tract infection aimed to reveal and identify possible markers of a host response on infection. A UPLC-MS based workflow, taking advantage of Ultra High Resolution (UHR) Qq-ToF-MS, and multivariate data handling were applied to a carefully selected group of 39 subjects with culture-confirmed febrile Escherichia coli UTI. Using a combination of unsupervised and supervised multivariate modeling we have pinpointed a number of peptides specific for UTI. An unequivocal structural identification of these peptides, as O-glycosylated fragments of the human fibrinogen alpha 1 chain, required MS2 and MS3 experiments on two different MS platforms: ESI-UHR-Qq-ToF and ESI-ion trap, a blast search and, finally, confirmation was achieved by matching experimental tandem mass spectra with those of custom synthesized candidate-peptides.In conclusion, exploiting non-targeted UPLC-MS based approach for the investigation of UTI related changes in urine, we have identified and structurally characterized unique O-glycopeptides, which are, to our knowledge, the first demonstration of O-glycosylation of human fibrinogen alpha 1-chain. 相似文献
79.
80.