全文获取类型
收费全文 | 748篇 |
免费 | 38篇 |
专业分类
786篇 |
出版年
2023年 | 9篇 |
2022年 | 20篇 |
2021年 | 31篇 |
2020年 | 12篇 |
2019年 | 9篇 |
2018年 | 23篇 |
2017年 | 17篇 |
2016年 | 25篇 |
2015年 | 37篇 |
2014年 | 41篇 |
2013年 | 51篇 |
2012年 | 74篇 |
2011年 | 81篇 |
2010年 | 44篇 |
2009年 | 27篇 |
2008年 | 52篇 |
2007年 | 59篇 |
2006年 | 29篇 |
2005年 | 33篇 |
2004年 | 29篇 |
2003年 | 22篇 |
2002年 | 27篇 |
2001年 | 3篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1977年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1964年 | 1篇 |
1954年 | 1篇 |
1952年 | 1篇 |
排序方式: 共有786条查询结果,搜索用时 0 毫秒
41.
Ilijin L Janković-Tomanić M Mitić M Vlahović M Lazarević J Perić-Maratuga V Prolić Z Nenadović V 《Folia biologica》2003,51(3-4):207-211
The response of Morimus funereus larvae to total starvation and refeeding with qualitatively different nutritive substrates (artificial diets supplemented with yeast as a source of B complex vitamins or with a digestibility reducer-tannic acid) was examined in this paper. Refeeding resulted in a compensatory increase of larval growth. Feeding and refeeding with qualitatively different nutritive substrates affected both quality and quantity of midgut and brain proteins. The observed differences suggest the possible switching of enzyme isoforms in M. funereus midgut and changes in synthesis/secretion of neurohormones, depending on food presence and its nutritional value. 相似文献
42.
43.
Chen C Ma J Lazic A Backovic M Colley KJ 《The Journal of biological chemistry》2000,275(18):13819-13826
The ST6Gal I is a sialyltransferase that functions in the late Golgi to modify the N-linked oligosaccharides of glycoproteins. The ST6Gal I is expressed as two isoforms with a single amino acid difference in their catalytic domains. The STcys isoform is stably retained in the cell and is predominantly found in the Golgi, whereas the STtyr isoform is only transiently localized in the Golgi and is cleaved and secreted from a post-Golgi compartment. These two ST6Gal I isoforms were used to explore the role of the bilayer thickness mechanism and oligomerization in Golgi localization. Analysis of STcys and STtyr proteins with longer transmembrane regions suggested that the bilayer thickness mechanism is not the predominant mechanism used for ST6Gal I Golgi localization. In contrast, the formation and quantity of Triton X-100-insoluble oligomers was correlated with the stable or transient localization of the ST6Gal I isoforms in the Golgi. Nearly 100% of the STcys and only 13% of the STtyr were found as Triton-insoluble oligomers when Golgi membranes of COS-1 cells expressing these proteins were solubilized at pH 6.3, the pH of the late Golgi. In contrast, both proteins were found in the soluble fraction when these membranes were solubilized at pH 8.0. Analysis of other mutants suggested that a conformational change in the catalytic domain rather than increased disulfide bond-based cross-linking is the basis for the increased ability of STcys protein to form oligomers and the stable localization of STcys protein in the Golgi. 相似文献
44.
Irena Trbojević-Akmačić Frano Vučković Marija Vilaj Andrea Skelin Lennart C. Karssen Jasminka Krištić Julija Jurić Ana Momčilović Jelena Šimunović Massimo Mangino Manuela De Gregori Maurizio Marchesini Concetta Dagostino Jerko Štambuk Mislav Novokmet Richard Rauck Yurii S. Aulchenko Dragan Primorac Gordan Lauc 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2124-2133
Background
Low back pain (LBP) is the symptom of a group of syndromes with heterogeneous underlying mechanisms and molecular pathologies, making treatment selection and patient prognosis very challenging. Moreover, symptoms and prognosis of LBP are influenced by age, gender, occupation, habits, and psychological factors. LBP may be characterized by an underlying inflammatory process. Previous studies indicated a connection between inflammatory response and total plasma N-glycosylation. We wanted to identify potential changes in total plasma N-glycosylation pattern connected with chronic low back pain (CLBP), which could give an insight into the pathogenic mechanisms of the disease.Methods
Plasma samples of 1128 CLBP patients and 760 healthy controls were collected in clinical centers in Italy, Belgium and Croatia and used for N-glycosylation profiling by hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) after N-glycans release, fluorescent labeling and clean-up. Observed N-glycosylation profiles have been compared with a cohort of 126 patients with acute inflammation that underwent abdominal surgery.Results
We have found a statistically significant increase in the relative amount of high-branched (tri-antennary and tetra-antennary) N-glycan structures on CLBP patients' plasma glycoproteins compared to healthy controls. Furthermore, relative amounts of disialylated and trisialylated glycan structures were increased, while high-mannose and glycans containing bisecting N-acetylglucosamine decreased in CLBP.Conclusions
Observed changes in CLBP on the plasma N-glycome level are consistent with N-glycosylation changes usually seen in chronic inflammation.General significance
To our knowledge, this is a first large clinical study on CLBP patients and plasma N-glycome providing a new glycomics perspective on potential disease pathology. 相似文献45.
Marija Brgles Pero Prebeg Tihana Kurtović Jelena Ranić Martina Marchetti-Deschmann Günter Allmaier 《Preparative biochemistry & biotechnology》2016,46(7):695-703
Tetanus toxoid (TTd) is a highly immunogenic, detoxified form of tetanus toxin, a causative agent of tetanus disease, produced by Clostridium tetani. Since tetanus disease cannot be eradicated but is easily prevented by vaccination, the need for the tetanus vaccine is permanent. The aim of this work was to investigate the possibility of optimizing TTd purification, i.e., ammonium sulfate precipitation process. The influence of the percentage of ammonium sulfate, starting amount of TTd, buffer type, pH, temperature, and starting purity of TTd on the purification process were investigated using optimal design for response surface models. Responses measured for evaluation of the ammonium sulfate precipitation process were TTd amount (Lf/mL) and total protein content. These two parameters were used to calculate purity (Lf/mgPN) and the yield of the process. Results indicate that citrate buffer, lower temperature, and lower starting amount of TTd result in higher purities of precipitates. Gel electrophoresis combined with matrix-assisted laser desorption ionization–mass spectrometric analysis of precipitates revealed that there are no inter-protein cross-links and that all contaminating proteins have pIs similar to TTd, so this is most probably the reason for the limited success of purification by precipitation. 相似文献
46.
Rode M Flezar MS Kogoj-Rode M Us-Krasovec M 《Analytical and quantitative cytology and histology / the International Academy of Cytology [and] American Society of Cytology》2006,28(5):262-268
OBJECTIVE: To analyze image cytometric chromatin changes reflected in nuclear texture features and DNA ploidy of oral lichen planus in relation to the normal buccal mucosa and buccal mucosa expressing malignancy-associated changes in cancer patients. STUDY DESIGN: Twenty-eight patients with the reticular form of oral lichen planus, with a follow-up period of 25 years, 50 healthy controls and 50 lung cancer patients were included in the study. Scrapings of buccal mucosa were suspended in transport medium. Monolayer filter preparations were Feulgen-thionin stained. Image cytometric analysis was performed by Cyto-Savant. RESULTS: All oral lichen planus specimens in our study were diploid. In univariate analysis, differences between the normal buccal mucosa and oral lichen planus were found in several nuclear texture features, which gave an 80% correct classification rate in multivariate analysis. In the second part of the study, the classifier that recognizes malignancy-associated changes on the buccal mucosa of patients with lung cancer correctly recognized > 80% of oral lichen planus samples as normal buccal mucosa. CONCLUSION: Our results indicate that chromatin changes in oral lichen planus exist compared to normal cells; however, the chromatin structure of the reticular form of oral lichen planus does not express malignancy-associated changes and is more similar to normal squamous cells. 相似文献
47.
Jokić M Brčić-Kostić K Stefulj J Catela Ivković T Božo L Gamulin M Kapitanović S 《DNA and cell biology》2011,30(10):771-776
Altered folate levels may play an important role in colon carcinogenesis. The aim of this study was to investigate the association of polymorphisms in key folate-metabolizing genes with susceptibility to sporadic colon cancer. Six common polymorphisms (two in MTHFR and one each in MTR, MTRR, RFC1, and DHFR genes) were genotyped in 300 healthy subjects and 300 colon cancer patients from Croatia. Obtained results indicate possible protective role of MTRR 66 AA in sporadic colon cancer (OR=0.655; 95% CI=0.441-0.973; p=0.04). Maximum-likelihood analysis of haplotypes revealed a linkage disequilibrium (LD) between the two investigated polymorphisms of the MTHFR gene (C677T and A1298C), both in the control and patient groups (p<0.01 for both). LD was also detected between MTRR A66G and MTHFR A1298C polymorphisms but only in a group of patients (p<0.01). A haplotype of A66G and A1298C polymorphisms, A/A, proved to be protective (OR=0.775; 95% CI=0.603-0.996; p=0.04), whereas haplotype A/G was a risk factor for colon cancer (OR=1.270; 95% CI=1.007-1.602; p=0.04). Contrary to some previous studies, single-locus analyses identified no polymorphisms associated with risk for colon cancer, but demonstrated a possible protective effect of MTRR 66 AA genotype. The detected significant LD between two loci (MTHFR A1298C and MTRR A66G) located on different chromosomes indicates a strong selective force as a mechanism for the maintenance of their linkage. Specific combinations of alleles of these two polymorphisms showed a protective but also a risk effect on colon cancer susceptibility. 相似文献
48.
49.
Jelena Djordjevic Ana Djordjevic Miroslav Adzic Marija B. Radojcic 《Cellular and molecular neurobiology》2010,30(5):693-700
Chronic neuroendocrine stress usually leads to the elevation of the stress hormones and increased metabolic rate, which is
frequently accompanied by oxidative damage to the CNS. In the present study we hypothesized that chronic psychosocial isolation
(CPSI) of male Wistar rats, characterized by decreased serum corticosterone (CORT), unaltered catecholamines (CTs), and low
blood glucose (GLU), may also promote oxidative imbalance in the CNS, by targeting antioxidant defense system. To test it,
we have examined the relation between these input signals and protein expression/activity of antioxidant enzymes (AOEs): superoxide
dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GLR) in the hippocampus (HIPPO)
of CPSI animals. We found that CPSI did not affect SODs or CAT, but decreased activity of GPx and compromised GLR, an enzyme
highly dependent on blood GLU for its substrate precursor. Further, we have tested whether the CPSI experience altered AOEs
response to a novelty stress, and found that it attenuated peroxide-metabolizing enzymes, CAT and GPx, and decreased GLR activity,
even though blood GLU was restored. The altered ratios of hippocampal AOEs in CPSI animals, which were worsened under the
combined stress conditions, may lead to the accumulation of peroxide products and oxidative imbalance. The mechanism by which
CPSI generate oxidative imbalance in the HIPPO is most likely based on poor systemic energy conditions set by this stress.
Such conditions may cause functional decline of CNS structures, such as HIPPO, and are likely to promote state linked to onset
of many mood disorders. 相似文献
50.
Kroata Hazler Pilepić Miranda Morović Filip Orač Marija Šantor Vanja Vejnović 《Biologia》2010,65(5):805-812
The chloroplast DNA of 43 species including 16 sections from the genus Hypericum was studied by PCR-RFLP analysis. The PCR-amplified products of four cpDNA regions, trnC-trnD, psbC-trnS, trnL-trnF and rbcL were digested with four restriction endonucleases. A high level of interspecific variation was detected while intraspecific
diversity was not observed. The resulting parsimony analysis indicated the monophyletic assemblage of the sections Androsaemum, Olympia, Drosocarpium and Trigynobrathys. Monophyly of Hypericum is weakly supported, but close relationships of H. perforatum and H. maculatum are indicated. The members of Ascyreia are weakly resolved, but clustering of H. kouytchense and H. oblongifolium is well supported, however, H. reptans is nested with Olympia. CpDNA profiles and the positions on the parsimony tree indicate that the chloroplast donor among the putative parents of
the hybrid species H. ×inodorum is H. androsaemum. 相似文献