全文获取类型
收费全文 | 838篇 |
免费 | 45篇 |
出版年
2023年 | 5篇 |
2022年 | 5篇 |
2021年 | 13篇 |
2020年 | 9篇 |
2019年 | 9篇 |
2018年 | 17篇 |
2017年 | 24篇 |
2016年 | 32篇 |
2015年 | 42篇 |
2014年 | 51篇 |
2013年 | 74篇 |
2012年 | 80篇 |
2011年 | 99篇 |
2010年 | 48篇 |
2009年 | 29篇 |
2008年 | 37篇 |
2007年 | 52篇 |
2006年 | 50篇 |
2005年 | 30篇 |
2004年 | 29篇 |
2003年 | 32篇 |
2002年 | 23篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 7篇 |
1993年 | 4篇 |
1992年 | 7篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1970年 | 1篇 |
1963年 | 1篇 |
排序方式: 共有883条查询结果,搜索用时 15 毫秒
11.
Alex Graça Contato Vanessa Kaplum Débora Botura Scariot Francielle Pelegrin Garcia Hugo Falzirolli Fábio Vandresen Tânia Ueda-Nakamura Sueli de Oliveira Silva Cleuza Conceição da Silva Celso Vataru Nakamura 《化学与生物多样性》2023,20(7):e202300523
Leishmaniasis is a tropical zoonotic disease. It is found in 98 countries, with an estimated 1.3 million people being affected annually. During the life cycle, the Leishmania parasite alternates between promastigote and amastigote forms. The first line treatment for leishmaniasis are the pentavalent antimonials, such as N-methylglucamine antimoniate (Glucantime®) and sodium stibogluconate (Pentostam®). These drugs are commonly related to be associated with dangerous side effects such as cardiotoxicity, nephrotoxicity, hepatotoxicity, and pancreatitis. Considering these aspects, this work aimed to obtain a new series of limonene-acylthiosemicarbazides hybrids as an alternative for the treatment of leishmaniasis. For this, promastigotes, axenic amastigotes, and intracellular amastigotes of Leishmania amazonensis were used in the antiproliferative assay; J774-A1 macrophages for the cytotoxicity assay; and electron microscopy techniques were performed to analyze the morphology and ultrastructure of parasites. ATZ−S-04 compound showed the best result in both tests. Its IC50, in promastigotes, axenic amastigotes and intracellular amastigotes was 0.35±0.08 μM, 0.49±0.06 μM, and 15.90±2.88 μM, respectively. Cytotoxicity assay determined a CC50 of 16.10±1.76 μM for the same compound. By electron microscopy, it was observed that ATZ−S-04 affected mainly the Golgi complex, in addition to morphological changes in promastigote forms of L. amazonensis. 相似文献
12.
Achiléa Lisboa Bittencourt Maria das Graças Santana Araujo Maria do Socorro Fontoura Paes 《Mycopathologia》1980,71(3):155-158
A case of a two-year-old boy with multiple subcutaneous lesions caused by Basidiobolus haptosporus is presented.The child had also a non-toxic familial goiter and clinical and radiological features of a pulmonary illness. The pulmonary manifestations only disappeared with the treatment with potassium iodide. The authors think that the pulmonary lesions must have arisen by direct spread of the fungus from the subcutaneous lesions of the chest. 相似文献
13.
X Gra?a L de Lecea M R el-Maghrabi J M Ure?a C Caellas J Carreras P Puigdomenech S J Pilkis F Climent 《The Journal of biological chemistry》1992,267(18):12797-12803
The primary sequence of maize 2,3-bisphosphoglycerate-independent phosphoglycerate mutase was deduced from cDNAs isolated from maize cDNA libraries by screening with specific antibodies to the cofactor-independent enzyme and from a maize genomic clone. The genomic clone provided the 5'-nucleotide sequence encoding the N-terminal amino acids which could not be obtained from the cDNA. Confirmation that the nucleotide sequence was for the cofactor-independent phosphoglycerate mutase was obtained by sequencing the peptides generated from cyanogen bromide cleavage of the purified protein. This is the first report of the amino acid sequence of a 2,3-bisphosphoglycerate cofactor-independent phosphoglycerate mutase, which consists of 559 amino acids and is twice the molecular size of the mammalian cofactor-dependent enzyme subunit. Analysis of the cofactor-independent phosphoglycerate mutase amino acid sequence revealed no identity with the cofactor-dependent mutase types. Northern blot analysis confirmed this difference since the maize cofactor-independent phosphoglycerate mutase cDNA did not hybridize with mRNA of the cofactor-dependent mutase. The lack of amino acid identity between cofactor-dependent and -independent enzymes is consistent with their different catalytic mechanisms and suggests that both enzymes are unrelated evolutionarily and arose from two independent ancestral genes. However, a constellation of residues which are involved in metal ion binding in various alkaline phosphatases is conserved in the maize cofactor-independent phosphoglycerate mutase, which suggests that the enzyme is a member of the alkaline phosphatase family of enzymes. 相似文献
14.
Summary Explants from petioles, folioles or hypocotyls ofOnonis natrix have been used for calli initiation. Hypocotyls inoculated on MS medium supplemented with 2% sucrose and 0.5 mg.1–1 2,4-D / 1 mg.1–1 Kin showed to be the best primary explant. Cell suspension cultures were established in MS basal medium supplemented with 2% sucrose, 0.5 mg.1–1 NAA or 2,4-D and 1 mg.1–1 Kin. Different subculturing periods, inoculum density, hormonal supplementation and sucrose concentration were assayed in order to obtain the best culture growth conditions. The optimal conditions were achieved with cultures initiated with 40 g.1–1 of initial inoculum, growing in MS basal medium supplemented with 4% sucrose, 0.5 mg.1–1 NAA and 1 mg.1–1 Kin subcultured every twelve days. Under these experimental conditions, the cultures showed a doubling time of 36.3 hours. 相似文献
15.
The value of Y-body study for assessment of stromal cell engraftment was analyzed in 25 patients submitted to allogeneic bone marrow transplantation (BMT) (sex-matched in 12 cases and sex-mismatched in 13). The study was performed weekly on bone marrow smears until day +35, and the results were compared with those obtained in a control group of 20 patients submitted to autologous BMT (12 males and 8 females). Engraftment of haemopoietic cells was documented in all cases. The results of Y-body study on the recipients' fibroblast cells showed a pattern identical to that observed prior to BMT, independent of donor's sex. On the other hand, there were no differences between allogeneic and autologous BMT recipients in regard to percentage of Y-body positive cells. These results indicate that in allogeneic BMT there is no engraftment of the fibroblastic component of bone marrow stroma. 相似文献
16.
I. V. Goldenkova-Pavlova S. A. Brouskin R. M. Abdeev E. V. Markarova S. G. Bigvava L. A. Radkevich H. A. Kurdanov Zh. M. Kozhekbaeva A. S. Glotov O. A. Gra A. S. Zasedatelev T. V. Nasedkina E. S. Piruzyan 《Russian Journal of Genetics》2006,42(8):947-953
The N-acetylation polymorphisms of volunteers from the Moscow population analyzed by phenotyping and genotyping have been compared. The ratios between the proportions of fast acetylators (FAs) and slow acetylators (SAs) estimated by phenotyping and genotyping do not differ significantly from each other (47 and 44%, respectively). The absolute acetylation rate widely varies in both FAs and SAs. The NAT2 genotype and allele frequencies in the population sample have been calculated. The most frequent alleles are NAT2*4 (a “fast” allele), NAT2*5, and NAT2*6 (“slow” alleles); the most frequent genotypes are NAT2*5/*5, NAT2*4/*6, and NAT2*4/*5. Comparative analysis of N-acetylation polymorphism estimated by phenotyping and genotyping in the same subjects has shown a complete concordance between the phenotype and genotype in only 62 out of 75 subjects (87%). Comparative characteristics and presumed applications of the two approaches (quantitative estimation of acetylation rate and qualitative determination of the acetylator genotype) to the identification of individual acetylation status are presented. 相似文献
17.
Zh. M. Kozhekbaeva A. S. Glotov O. A. Gra I. V. Goldenkova-Pavlova S. A. Bruskin E. E. Agafonova E. V. Markarova R. M. Abdeev I. M. Korsunskaya A. L. Piruzyan V. E. Barsky A. S. Zasedatelev T. V. Nasedkina 《Molecular Biology》2007,41(4):656-664
The NAT2 product, N-acetyltransferase 2, is involved in biotransformation and detoxification of several aromatic amines (in particular, 2-aminofluorene, 4-aminobiphenyl, and 4-naphthylamine), which are strongly mutagenic and carcinogenic, and acetylates some drugs, affecting their metabolism. A biological microchip was developed to detect 16 point mutations, which determine 36 alleles and 660 genotypes of NAT2. The genotypes can be divided into four groups according to the acetylator phenotype: groups with rapid (R/R), intermediate (R/S), or slow (S/S) acetylation and a group combining intermediate and slow alleles (“R/S or S/S”). The last group includes the alleles determined by combinations of seven mutations (191G/A, 282C/T, 341T/C, 481C/T, 590G/A, 803A/G, and 857G/A), whose cis or trans position is detectable by restriction enzyme analysis. The NAT2 genotype was unequivocally established for 37 out of 71 DNA specimens, while the other 34 specimens were characterized by more than two genotypes. By the acetylator phenotype, 16 out of the 34 genotypes were assigned to the group “R/S or S/S,” combining mutations 282C/T, 341T/C, 481C/T, 590G/A, and 803A/G. Thus, the biochip allows primary analysis of most NAT2 polymorphic substitutions, the acetylator genotype being important to know in predictive medicine and individualized therapy. 相似文献
18.
Batista MN Cuppari L de Fátima Campos Pedrosa L Almeida Md de Almeida JB de Medeiros AC Canziani ME 《Biological trace element research》2006,112(1):1-12
The aim of this study was to compare the nutritional status of zinc and copper in patients with and without diabetes submitted
to chronic hemodialysis. Thirty-three patients with type 2 diabetes (DM group), 30 nondiabetic patients (NDM group), and 20
healthy individuals (control group) were studied. Plasma, erythrocyte, and urinary zinc and plasma copper were obtained from
atomic absorption spectrophotometry and ceruloplasmin by immunonephelometry. The anthropometric parameters were similar among
the groups. Plasma zinc was lower and erythrocyte zinc was higher in the DM and NDM groups in relation to the control group.
No difference in urinary zinc was observed comparing the groups. Plasma copper was higher in the DM group when compared to
the NDM and control groups. Ceruloplasmin was similar in the three groups. Serum urea was a positive independent determinant
of plasma zinc concentrations. The determinants of erythrocyte zinc were MAMC midarm nuscle circumference and Kt/V dialysis
adequacy. The determinants of plasma copper concentration were serum creatinine and serum glucose. The results of this study
demonstrate an alteration in the distribution of zinc of patients with chronic kidney disease (CKD) independently of the presence
of DM. Also, the status of copper seems not to be influenced by CKD, but only by the metabolic derangements associated with
diabetes. 相似文献
19.
Graça Soveral Catarina Prista Teresa F. Moura Maria C. Loureiro‐Dias 《Biology of the cell / under the auspices of the European Cell Biology Organization》2011,103(1):35-54
In yeast, the presence of orthodox aquaporins has been first recognized in Saccharomyces cerevisiae, in which two genes (AQY1 and AQY2) were shown to be related to mammal and plant water channels. The present review summarizes the putative orthodox aquaporin protein sequences found in available genomes of yeast and filamentous fungi. Among the 28 yeast genomes sequenced, most species present only one orthodox aquaporin, and no aquaporins were found in eight yeast species. Alignment of amino acid sequences reveals a very diverse group. Similarity values vary from 99% among species within the Saccharomyces genus to 34% between ScAqy1 and the aquaporin from Debaryomyces hansenii. All of the fungal aquaporins possess the known characteristic sequences, and residues involved in the water channel pore are highly conserved. Advances in the establishment of the structure are reviewed in relation to the mechanisms of selectivity, conductance and gating. In particular, the involvement of the protein cytosolic N‐terminus as a channel blocker preventing water flow is addressed. Methodologies used in the evaluation of aquaporin activity frequently involve the measurement of fast volume changes. Particular attention is paid to data analysis to obtain accurate membrane water permeability parameters. Although the presence of aquaporins clearly enhances membrane water permeability, the relevance of these ubiquitous water channels in yeast performance remains obscure. 相似文献
20.
Hanna Grajek Regina Drabent Grażyna Żurkowska Czesław Bojarski 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,801(3):456-460
The electronic absorption spectra of the flavomononucleotide (FMN) in aqueous solution and in glycerine-water solution with change of the dye concentration have been measured. The FMN dimer absorption spectrum, monomer absorption spectrum, dimerization constant K and molar fraction of the monomer were calculated. It was found that FMN dimerization constants in aqueous solution were Ka = 118.0 l/mol and in glycerine Kg = 20.5 l/mol. In the region of the monomer absorption band two dimer absorption bands appear, in accordance with the Kasha molecular exciton theory. 相似文献