全文获取类型
收费全文 | 20219篇 |
免费 | 1549篇 |
国内免费 | 146篇 |
专业分类
21914篇 |
出版年
2023年 | 189篇 |
2022年 | 195篇 |
2021年 | 385篇 |
2020年 | 345篇 |
2019年 | 333篇 |
2018年 | 670篇 |
2017年 | 581篇 |
2016年 | 664篇 |
2015年 | 677篇 |
2014年 | 754篇 |
2013年 | 1156篇 |
2012年 | 1650篇 |
2011年 | 1816篇 |
2010年 | 935篇 |
2009年 | 698篇 |
2008年 | 1422篇 |
2007年 | 1391篇 |
2006年 | 1332篇 |
2005年 | 1122篇 |
2004年 | 1132篇 |
2003年 | 1045篇 |
2002年 | 841篇 |
2001年 | 226篇 |
2000年 | 299篇 |
1999年 | 192篇 |
1998年 | 108篇 |
1997年 | 96篇 |
1996年 | 85篇 |
1995年 | 92篇 |
1994年 | 91篇 |
1993年 | 84篇 |
1992年 | 96篇 |
1991年 | 79篇 |
1990年 | 70篇 |
1989年 | 61篇 |
1988年 | 48篇 |
1987年 | 55篇 |
1986年 | 43篇 |
1985年 | 49篇 |
1984年 | 66篇 |
1983年 | 44篇 |
1982年 | 60篇 |
1981年 | 53篇 |
1980年 | 65篇 |
1979年 | 47篇 |
1978年 | 49篇 |
1977年 | 37篇 |
1976年 | 47篇 |
1975年 | 45篇 |
1974年 | 48篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
111.
Marie-Dominique Rhoda-Hardy-Dessources René-Serge de Neef Guy Mérault Françoise Giraud 《生物化学与生物物理学报:疾病的分子基础》1993,1181(1):90-96
PtdIns and PtdInsP kinases from normal erythrocyte (AA) membranes and sickle cell anaemia erythrocyte (SS) membranes have been characterized. PtdIns kinase was studied in native membranes under conditions in which PtdInsP kinase and PtdInsP phosphatase do not express any activity. Kinetic analysis of the AA and SS PtdIns kinases indicate similar Km values for PtdIns and ATP but higher Vmax values for SS PtdIns kinase. PtdInsP kinase was partially purified from erythrocyte ghosts by NaCl extraction. The kinetic parameters of PtdInsP kinase determined under these conditions were similar in AA and SS NaCl extracts. These data suggest the presence of some effector of PtdIns kinase in SS cell membranes, resulting in a greater activity of the enzyme. This leads consequently, to increase the PtdInsP pool and to activate PtdInsP kinase, in agreement with our previous observations of a greater [32P]Pi incorporation in both polyphosphoinositides in SS cells relatively to AA cells. 相似文献
112.
Béatrice Drouet Luis Garcia Dominique Simon-Chazottes Marie Geneviève Mattei Jean-Louis Guénet Arnold Schwartz Gyula Varadi Martine Pinçon-Raymond 《Mammalian genome》1993,4(9):499-503
Using both chromosomal in situ hybridization and molecular techniques, we report the genetic localization of the gene coding for the alpha 1 subunit of the skeletal slow Ca2+ current channel/DHP receptor gene (Cchl1a3) on human Chromosome (Chr) 1 (1q31–1q32 region) and on mouse Chr 1 region (F-G). On the basis of single-strand conformation polymorphism (SSCP-PCR) analysis in an interspecific backcross, we have determined that the Cchl1a3=mdg (muscular dysgenesis) locus is very closely linked to the myogenin (Myog) locus. 相似文献
113.
Crystalline bacterial cell surface layers 总被引:17,自引:2,他引:15
Crystalline arrays of proteinaceous subunits forming surface layers (S-layers) are one of the most commonly observed prokaryotic cell envelope structures. They are ubiquitous amongst Gram-positive and Gram-negative archaeobacteria and eubacteria and, if present, account for the major protein species produced by the cells. S-layers can provide organisms with a selection advantage by providing various functions including protective coats, molecular sieves, ion traps and structures involved in cell surface interactions. S-layers were identified as contributing to virulence when present as a structural component of pathogens. In Gram-negative archaeobacteria they are involved in determining cell shape and cell division. The crystalline arrays reveal a broad-application potential in biotechnology, vaccine development and molecular nanotechnology. 相似文献
114.
Işıl Nihan Korkmaz Uğur Güller Ramazan Kalın Hasan Özdemir Ömer İrfan Küfrevioğlu 《化学与生物多样性》2023,20(5):e202201220
A thiol compound, glutathione, is essential for healthy cell defence against xenobiotics and oxidative stress. Glutathione reductase (GR) and glutathione S-transferase (GST) are two glutathione-related enzymes that function in the antioxidant and the detoxification systems. In this study, potential inhibitory effects of methyl 4-aminobenzoate derivatives on GR and GST were examined in vitro. GR and GST were isolated from human erythrocytes with 7.63 EU/mg protein and 5.66 EU/mg protein specific activity, respectively. It was found that compound 1 (methyl 4-amino-3-bromo-5-fluorobenzoate with Ki value of 0.325±0.012 μM) and compound 5 (methyl 4-amino-2-nitrobenzoate with Ki value of 92.41±22.26 μM) inhibited GR and GST stronger than other derivatives. Furthermore, a computer-aided method was used to predict the binding affinities of derivatives, ADME characteristics, and toxicities. Derivatives 4 (methyl 4-amino-2-bromobenzoate) and 6 (methyl 4-amino-2-chlorobenzoate) were estimated to have the lowest binding energies into GR and GST receptors, respectively according to results of in silico studies. 相似文献
115.
Prof. Christchellyn Klegin Prof. Dr. Eduardo Miranda Ethur Bárbara Buhl Ana Caroline Giacomin Prof. Dr. Juçara Bordin Prof. Dr. Neusa Fernandes de Moura Matheus Henrique Oliveira de Sousa 《化学与生物多样性》2023,20(6):e202300253
The present study aimed to examine the phenolic content and evaluate the antimicrobial and antioxidant potential of ethanol extracts from the moss species Phyllogonium viride Brid. on the pathogenic bacteria Salmonella enterica serovar enteritidis, Staphylococcus aureus, Listeria monocytogenes and Escherichia coli, and the pathogenic fungi Candida albicans and Cryptococcus neoformans. The antimicrobial activity was determined from Minimum Inhibitory Concentration (MIC) Minimum Bactericidal Concentration (MBC) and Minimum Fungicidal Concentration (MFC). Antioxidant activity was determined by the DPPH method. Folin-Denis reagent was used for the content of total phenolics and flavonoids and HPLC-DAD for identification of phenolic compounds. The results showed that bacteriostatic and bactericidal activities occurred at concentrations ranging from 9.76 μg/mL–78.13 μg/mL among all evaluated microorganisms. These values, considering the criteria used, suggest the P. viride extract as a potent antimicrobial. For antioxidant activity, P. viride extract was considered weak. Analysis of the phenolic content showed a wide range of compounds, with Kaempferol (0.41 mg/g) being the major compound, followed by t-cinnamic acid and caffeic acid (0.17 mg/g). Although P. viride is a species of moss not yet referenced in scientific publications of biotechnological interest, it has shown promising potential for further studies and possible application as an antimicrobial of natural origin. 相似文献
116.
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
117.
Prof. Dr. Mehmet Emin Duru Büşra Eroğlu Assoc. Prof. Dr. Gülsen Tel-Çayan Meltem Taş-Küçükaydın Dr. Selçuk Küçükaydın Dr. Fatih Çayan Prof. Dr. Özgür Ceylan 《化学与生物多样性》2023,20(6):e202300486
Sunflower honey (SH) is bright yellow, fragrant, pollen-flavoured, slightly herbaceous and has a unique taste. The present research aims to examine the enzyme inhibitory, antioxidant, anti-inflammatory, antimicrobial and anti-quorum sensing activities and phenolic compositions of 30 sunflower honeys (SHs) produced from several regions of Turkey with chemometric study. SAH from Samsun exhibited the best antioxidant activity in β-carotene linoleic acid (IC50: 7.33±0.17 mg/mL) and CUPRAC (A0.50: 4.94±0.13 mg/mL) assays, anti-urease activity (60.63±0.87 %) and anti-inflammatory activity against COX-1 (73.94±1.08 %) and COX-2 (44.96±0.85 %). SHs exhibited mild antimicrobial activity against the test microorganisms while they showed high quorum sensing inhibition zones measured in the range of 42–52 mm against the CV026 strain. The phenolic composition was determined by high performance liquid chromatography with diode array detection (HPLC-DAD) system and levulinic, gallic, p-hydroxybenzoic, vanillic and p-coumaric acids were identified in all studied SHs. The classification of SHs was performed the using PCA and HCA. This study revealed that phenolic compounds and biological properties are effective in classification of SHs according to their geographical origin. The results suggest that studied SHs could be valued as potential agents with versatile bioactivities in oxidative stress-related disease, microbial infections, inflammation, melanoma, and peptic ulcer. 相似文献
118.
In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH4, the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by 1H-NMR, 13C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC50 values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC50 values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol ( 4 d ) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol ( 7 d ) were determined to be 18.1 μg and 35.1 μg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship. 相似文献
119.
Jérémy Gauthier Joana Meier Fabrice Legeai Melanie McClure Annabel Whibley Anthony Bretaudeau Hélène Boulain Hugues Parrinello Sam T. Mugford Richard Durbin Chenxi Zhou Shane McCarthy Christopher W. Wheat Florence Piron-Prunier Christelle Monsempes Marie-Christine François Paul Jay Camille Noûs Emma Persyn Emmanuelle Jacquin-Joly Camille Meslin Nicolas Montagné Claire Lemaitre Marianne Elias 《Molecular ecology resources》2023,23(4):872-885
The ithomiine butterflies (Nymphalidae: Danainae) represent the largest known radiation of Müllerian mimetic butterflies. They dominate by number the mimetic butterfly communities, which include species such as the iconic neotropical Heliconius genus. Recent studies on the ecology and genetics of speciation in Ithomiini have suggested that sexual pheromones, colour pattern and perhaps hostplant could drive reproductive isolation. However, no reference genome was available for Ithomiini, which has hindered further exploration on the genetic architecture of these candidate traits, and more generally on the genomic patterns of divergence. Here, we generated high-quality, chromosome-scale genome assemblies for two Melinaea species, M. marsaeus and M. menophilus, and a draft genome of the species Ithomia salapia. We obtained genomes with a size ranging from 396 to 503 Mb across the three species and scaffold N50 of 40.5 and 23.2 Mb for the two chromosome-scale assemblies. Using collinearity analyses we identified massive rearrangements between the two closely related Melinaea species. An annotation of transposable elements and gene content was performed, as well as a specialist annotation to target chemosensory genes, which is crucial for host plant detection and mate recognition in mimetic species. A comparative genomic approach revealed independent gene expansions in ithomiines and particularly in gustatory receptor genes. These first three genomes of ithomiine mimetic butterflies constitute a valuable addition and a welcome comparison to existing biological models such as Heliconius, and will enable further understanding of the mechanisms of adaptation in butterflies. 相似文献
120.
Coelho-Rocha Nina Dias de Jesus Luís Cláudio Lima Barroso Fernanda Alvarenga Lima da Silva Tales Fernando Ferreira Enio Gonçalves José Eduardo dos Santos Martins Flaviano de Oliveira Carvalho Rodrigo Dias Barh Debmalya Azevedo Vasco Ariston de Carvalho 《Probiotics and antimicrobial proteins》2023,15(1):160-174
Probiotics and Antimicrobial Proteins - Beneficial effects of Lactiplantibacillus plantarum strains have been widely reported. Knowing that the effects of probiotic bacteria are strain-dependent,... 相似文献