全文获取类型
收费全文 | 1050篇 |
免费 | 64篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 4篇 |
2021年 | 29篇 |
2020年 | 15篇 |
2019年 | 15篇 |
2018年 | 22篇 |
2017年 | 14篇 |
2016年 | 33篇 |
2015年 | 43篇 |
2014年 | 56篇 |
2013年 | 80篇 |
2012年 | 95篇 |
2011年 | 91篇 |
2010年 | 44篇 |
2009年 | 47篇 |
2008年 | 60篇 |
2007年 | 58篇 |
2006年 | 73篇 |
2005年 | 64篇 |
2004年 | 65篇 |
2003年 | 60篇 |
2002年 | 34篇 |
2001年 | 8篇 |
2000年 | 6篇 |
1999年 | 11篇 |
1998年 | 14篇 |
1997年 | 5篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1978年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 4篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1962年 | 4篇 |
1955年 | 3篇 |
排序方式: 共有1115条查询结果,搜索用时 281 毫秒
41.
ngel A. del Río‐Chvez Hugo A. García‐Gutirrez Luisa U. Romn‐Marín Lidia Beiza‐Granados Carlos M. Cerda‐García‐Rojas Pedro Joseph‐Nathan Juan D. Hernndez‐Hernndez 《Chirality》2019,31(11):934-946
The epimeric diterpenes (+)‐(1S,3E,7E,11S,12S)‐verticilla‐3,7‐dien‐12‐ol ( 1 ), isolated from Bursera suntui, and (+)‐(1S,3E,7E,11S,12R)‐verticilla‐3,7‐dien‐12‐ol ( 2 ), isolated from Bursera kerberi, gave the same Wagner‐Meerwein rearrangement product (?)‐(1E,4Z,8Z,11S,12R)‐phomacta‐1,(15)4,8‐triene ( 3 ). The Et2O:BF3‐induced transformations evidence that verticillenes and phomactanes, both containing the bicyclo[9.3.1]pentadecane skeleton, are biogenetically related through the verticillen‐12‐yl cation ( A + ), which also is a key intermediate in the biosynthetic pathways to generate antitumor taxanes. Molecular modeling using the Monte Carlo protocol, followed by density functional theory (DFT) geometry optimization employing the hybrid functionals B3LYP and B3PW91, both with the DGDZVP basis set, secured the configuration of 3 as followed from the good agreement between the calculated and experimental vibrational circular dichroism spectra. Similar DFT calculations allowed determining the absolute configuration of (+)‐(1R,4R,5R,8S,9S,11S,12R,15R)‐1,15:4,5:8,9‐triepoxyphomactane ( 9 ), which surprisingly derives from epoxidation of the second minimum energy conformer of 3 . 相似文献
42.
PCR-based genomic fingerprinting by use of enterobacterial repetitive intergenic consensus primers (ERIC-PCR) was evaluated
for its use in fingerprinting DNA of mixed Gram-negative bacterial strains and BIOLOG Gram-negative (GN) microplate substrate
communities. ERIC-PCR fingerprints of six different pure bacterial strains and a combined mixture of the strains were compared
with fingerprints obtained by two more established methods: amplified ribosomal DNA restriction analysis (ARDRA) and random
amplified polymorphic DNA analysis (RAPD-PCR). The ERIC-PCR fingerprint of the mixed strains was highly reproducible and was
more species-specific and representative of the individual strain fingerprints than the ARDRA and RAPD-PCR fingerprints, respectively.
ERIC-PCR fingerprinting of model and rhizosphere BIOLOG GN substrate communities also provided clearly distinguishable fingerprints.
Results of this study suggest that ERIC-PCR represents a rapid and highly discriminating method for fingerprinting DNA of
mixed Gram-negative bacterial strains and BIOLOG GN substrate communities.
Received: 11 September 1998 / Accepted: 29 October 1998 相似文献
43.
Cimato AN Piehl LL Facorro GB Torti HB Hager AA 《Free radical biology & medicine》2004,37(12):2042-2051
Liposomes are today useful tools in different fields of science and technology. A lack of stability due to lipid peroxidation is the main problem in the extension of the use of these formulations. Recent investigative works have reported the protective effects of stable nitroxide radicals against oxidative processes in different media and under different stress conditions. Our group has focused its attention on the natural aging of liposomes and the protection provided by the water- and lipid-soluble nitroxide radicals 2,2,6,6-tetramethylpiperdine-1-oxyl (TEMPO) and doxylstearic acids (5-DSA, 12-DSA, and 16-DSA), respectively. Unilamellar liposomes were incubated under air atmosphere at 37°C, both in the absence and in the presence of these radicals. Conjugated dienes, lipid hydroperoxides, TBARS, membrane fluidity, and nitroxide ESR signal intensity were followed as a function of time. Our results demonstrated that doxylstearic acids were more efficient than TEMPO in retarding lipid peroxidation at all the concentrations tested. The inhibition percentages, depending on the total nitroxide concentration, were not proportional to the lipid–water partition coefficient. Furthermore, time-course ESR signals showed a slower decrease for doxylstearic acids than for TEMPO. No significant differences were found among 5-DSA, 12-DSA, and 16-DSA. We concluded that the nitroxide radical efficiency as antioxidant directly depends on both nitroxide concentration and lipophilicity. 相似文献
44.
Montes-Horcasitas C Ruiz-Medrano R Magaña-Plaza I Silva LG Herrera-Martínez A Hernández-Montalvo L Xoconostle-Cázares B 《Current microbiology》2004,49(6):428-432
The conjugative self-transmissible plasmid pHT73, harbored in Bacillus thuringiensis var. kurstaki, was demonstrated to be transferred to Cellulomonas flavigena, a cellulolytic bacterium. Both conjugation and transformation procedures yielded resistant colonies; however, chromosomal integration was observed only when bacterial conjugation occurred. The efficiency of conjugation was 10% of recipient strain, which is considered a very efficient process. When the plasmid pHT73 was introduced by transformation, erythromycin-resistant cells contained the plasmid as an episome with no arrangements, as assayed by Southern blot analysis. In contrast, conjugated-resistant cells harbor the plasmid integrated into the chromosome. These data suggest a common mechanism of cell communication between nonrelated bacterial species with similar ecological habitats, and also that both electroporation and conjugation can be used to transform C. flavigena efficiently. 相似文献
45.
Molecular mechanism of thyroid hormone action 总被引:1,自引:0,他引:1
46.
Glutamine (Gln), glutamate (Glu) and gamma-amino butyric acid (GABA) are essential amino acids for brain metabolism and function. Astrocytic-derived glutamine is the precursor of the two most important neurotransmitters: glutamate, an excitatory neurotransmitter, and GABA, an inhibitory neurotransmitter. In addition to their roles in neurotransmission these neurotransmitters act as alternative metabolic substrates that enable metabolic coupling between astrocytes and neurons. The relationships between Gln, Glu and GABA were studied under lead (Pb) toxicity conditions using synaptosomal fractions obtained from adult rat brains to investigate the cause of Pb neurotoxicity-induced seizures. We have found that diminished transport of [(14)C]GABA occurs after Pb treatment. Both uptake and depolarization-evoked release decrease by 40% and 30%, respectively, relative to controls. Lower expression of glutamate decarboxylase (GAD), the GABA synthesizing enzyme, is also observed. In contrast to impaired synaptosomal GABA function, the GABA transporter GAT-1 protein is overexpressed (possibly as a compensative mechanism). Furthermore, similar decreases in synaptosomal uptake of radioactive glutamine and glutamate are observed. However, the K(+)-evoked release of Glu increases by 20% over control values and the quantity of neuronal EAAC1 transporter for glutamate reaches remarkably higher levels after Pb treatment. In addition, Pb induces decreased activity of phosphate-activated glutaminase (PAG), which plays a role in glutamate metabolism. Most noteworthy is that the overexpression and reversed action of the EAAC1 transporter may be the cause of the elevated extracellular glutamate levels. In addition to the impairment of synaptosomal processes of glutamatergic and GABAergic transport, the results indicate perturbed relationships between Gln, Glu and GABA that may be the cause of altered neuronal-astrocytic interactions under conditions of Pb neurotoxicity. 相似文献
47.
Hu YJ Dolan ME Bae R Yee H Roy M Glickman R Kiremidjian-Schumacher L Diamond AM 《Biological trace element research》2004,101(2):97-106
Glutathione peroxidase is a selenium-containing, antioxidant enzyme previously implicated in the risk and development of lung
and breast cancer, in part the result of allelic loss at the GPx-1 locus. This study examined allelic loss at the same locus in squamous cell carcinomas of the head and neck. The frequency
of a polymorphism at codon 198 resulting in either a leucine or a proline at that position was surveyed by comparing 133 DNA
samples obtained from head and neck tumors and 517 samples obtained from cancer-free individuals. Tumor DNAs exhibited fewer
pro/leu heterozygotes as compared to DNA obtained from the cancer-free population. Fewer GPx-1 heterozygotes were verified by determining the frequency of highly polymorphic alanine repeat sequences in the same gene.
The analysis revealed an approximately 42% reduction in heterozygosity in the DNA from the tumor samples. In order to assess
loss of heterozygosity (LOH) at the GPx-1 locus, DNA was genotyped from peripheral lymphocytes, tumor tissue, and microscopically normal tissues adjacent to the tumor,
derived from the same patients. These studies indicated LOH at the GPx-1 locus in each of the three tumor/normal tissues sample sets examined. Furthermore, LOH in the microscopically normal tissues
at the tumor margin occurred in two of the three sample sets examined. These data implicate GPx-1 in the development of squamous cell carcinoma the head and neck and suggest that allelic loss of this gene, or one tightly
linked to it, is an early event in the development of this type of malignancy.
Author to whom all correspondence and reprint requests should be addressed. These authors contributed equally to this work. 相似文献
48.
Atwal KS Ahmad S Ding CZ Stein PD Lloyd J Hamann LG Green DW Ferrara FN Wang P Rogers WL Doweyko LM Miller AV Bisaha SN Schmidt JB Li L Yost KJ Lan HJ Madsen CS 《Bioorganic & medicinal chemistry letters》2004,14(4):1027-1030
A series of substituted guanidine derivatives were prepared and evaluated as potent and selective inhibitors of mitochondrial F(1)F(0) ATP hydrolase. The initial thiourethane derived lead molecules possessed intriguing in vitro pharmacological profiles, though contained moieties considered non-drug-like. Analogue synthesis efforts led to compounds with maintained potency and superior physical properties. Small molecules in this series which potently and selectivity inhibit ATP hydrolase and not ATP synthase may have utility as cardioprotective agents. 相似文献
49.
Jennings LD Foreman KW Rush TS Tsao DH Mosyak L Kincaid SL Sukhdeo MN Sutherland AG Ding W Kenny CH Sabus CL Liu H Dushin EG Moghazeh SL Labthavikul P Petersen PJ Tuckman M Haney SA Ruzin AV 《Bioorganic & medicinal chemistry》2004,12(19):5115-5131
The ZipA-FtsZ protein-protein interaction is a potential target for antibacterial therapy. The design and parallel synthesis of a combinatorial library of small molecules, which target the FtsZ binding area on ZipA are described. Compounds were demonstrated to bind to the FtsZ binding domain of ZipA by HSQC NMR and to inhibit cell division in a cell elongation assay. 相似文献
50.