全文获取类型
收费全文 | 1811篇 |
免费 | 126篇 |
国内免费 | 44篇 |
出版年
2024年 | 7篇 |
2023年 | 21篇 |
2022年 | 37篇 |
2021年 | 75篇 |
2020年 | 35篇 |
2019年 | 40篇 |
2018年 | 75篇 |
2017年 | 46篇 |
2016年 | 63篇 |
2015年 | 89篇 |
2014年 | 107篇 |
2013年 | 141篇 |
2012年 | 169篇 |
2011年 | 165篇 |
2010年 | 79篇 |
2009年 | 78篇 |
2008年 | 98篇 |
2007年 | 83篇 |
2006年 | 79篇 |
2005年 | 85篇 |
2004年 | 72篇 |
2003年 | 65篇 |
2002年 | 52篇 |
2001年 | 29篇 |
2000年 | 31篇 |
1999年 | 15篇 |
1998年 | 11篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 5篇 |
1993年 | 10篇 |
1992年 | 9篇 |
1991年 | 19篇 |
1990年 | 5篇 |
1989年 | 14篇 |
1987年 | 9篇 |
1986年 | 6篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有1981条查询结果,搜索用时 62 毫秒
41.
42.
Sai Krishna C. Korada Trevor D. Johns Christopher E. Smith Nathan D. Jones Kimberly A. McCabe Charles E. Bell 《Nucleic acids research》2013,41(11):5887-5897
Escherichia coli Exonuclease I (ExoI) digests single-stranded DNA (ssDNA) in the 3′-5′ direction in a highly processive manner. The crystal structure of ExoI, determined previously in the absence of DNA, revealed a C-shaped molecule with three domains that form a central positively charged groove. The active site is at the bottom of the groove, while an extended loop, proposed to encircle the DNA, crosses over the groove. Here, we present crystal structures of ExoI in complex with four different ssDNA substrates. The structures all have the ssDNA bound in essentially the predicted manner, with the 3′-end in the active site and the downstream end under the crossover loop. The central nucleotides of the DNA form a prominent bulge that contacts the SH3-like domain, while the nucleotides at the downstream end of the DNA form extensive interactions with an ‘anchor’ site. Seven of the complexes are similar to one another, but one has the ssDNA bound in a distinct conformation. The highest-resolution structure, determined at 1.95 Å, reveals an Mg2+ ion bound to the scissile phosphate in a position corresponding to MgB in related two-metal nucleases. The structures provide new insights into the mechanism of processive digestion that will be discussed. 相似文献
43.
44.
Anbarasi Kothandapani Akshada Sawant Venkata Srinivas Mohan Nimai Dangeti Robert W. Sobol Steve M. Patrick 《Nucleic acids research》2013,41(15):7332-7343
Base excision repair (BER) and mismatch repair (MMR) pathways play an important role in modulating cis-Diamminedichloroplatinum (II) (cisplatin) cytotoxicity. In this article, we identified a novel mechanistic role of both BER and MMR pathways in mediating cellular responses to cisplatin treatment. Cells defective in BER or MMR display a cisplatin-resistant phenotype. Targeting both BER and MMR pathways resulted in no additional resistance to cisplatin, suggesting that BER and MMR play epistatic roles in mediating cisplatin cytotoxicity. Using a DNA Polymerase β (Polβ) variant deficient in polymerase activity (D256A), we demonstrate that MMR acts downstream of BER and is dependent on the polymerase activity of Polβ in mediating cisplatin cytotoxicity. MSH2 preferentially binds a cisplatin interstrand cross-link (ICL) DNA substrate containing a mismatch compared with a cisplatin ICL substrate without a mismatch, suggesting a novel mutagenic role of Polβ in activating MMR in response to cisplatin. Collectively, these results provide the first mechanistic model for BER and MMR functioning within the same pathway to mediate cisplatin sensitivity via non-productive ICL processing. In this model, MMR participation in non-productive cisplatin ICL processing is downstream of BER processing and dependent on Polβ misincorporation at cisplatin ICL sites, which results in persistent cisplatin ICLs and sensitivity to cisplatin. 相似文献
45.
46.
47.
Gudrun Lisa Bovenkamp Ulrike Zanzen Katla Sai Krishna Josef Hormes Alexander Prange 《Applied and environmental microbiology》2013,79(20):6385-6390
Silver ions are widely used as antibacterial agents, but the basic molecular mechanism of this effect is still poorly understood. X-ray absorption near-edge structure (XANES) spectroscopy at the Ag LIII, S K, and P K edges reveals the chemical forms of silver in Staphylococcus aureus and Escherichia coli (Ag+ treated). The Ag LIII-edge XANES spectra of the bacteria are all slightly different and very different from the spectra of silver ions (silver nitrate and silver acetate), which confirms that a reaction occurs. Death or inactivation of bacteria was observed by plate counting and light microscopy. Silver bonding to sulfhydryl groups (Ag-S) in cysteine and Ag-N or Ag-O bonding in histidine, alanine, and dl-aspartic acid was detected by using synthesized silver-amino acids. Significantly lower silver-cysteine content, coupled with higher silver-histidine content, in Gram-positive S. aureus and Listeria monocytogenes cells indicates that the peptidoglycan multilayer could be buffering the biocidal effect of silver on Gram-positive bacteria, at least in part. Bonding of silver to phosphate groups was not detected. Interaction with DNA or proteins can occur through Ag-N bonding. The formation of silver-cysteine can be confirmed for both bacterial cell types, which supports the hypothesis that enzyme-catalyzed reactions and the electron transport chain within the cell are disrupted. 相似文献
48.
Smitha Surendran Thamarath A. Alia Esha Roy Karthick Babu Sai Sankar Gupta John H. Golbeck Jörg Matysik 《Photosynthesis research》2013,117(1-3):461-469
The solid-state photo-CIDNP (photochemically induced dynamic nuclear polarization) effect is studied in photosynthetic reaction centers of Heliobacillus mobilis at different magnetic fields by 13C MAS (magic-angle spinning) NMR spectroscopy. Two active states of heliobacterial reaction centers are probed: an anaerobic preparation of heliochromatophores (“Braunstoff”, German for “brown substance”) as well as a preparation of cells after exposure to oxygen (“Grünstoff”, “green substance”). Braunstoff shows significant increase of enhanced absorptive (positive) signals toward lower magnetic fields, which is interpreted in terms of an enhanced differential relaxation (DR) mechanism. In Grünstoff, the signals remain emissive (negative) at two fields, confirming that the influence of the DR mechanism is comparably low. 相似文献
49.
Nupur Bhumika Vaidya Naga Radha Srinivas Tanuku Anil Kumar Pinnaka 《Antonie van Leeuwenhoek》2013,103(2):347-355
A novel marine, Gram-negative, rod-shaped bacterium, designated strain N9T, was isolated from a water sample of the sea shore at Visakhapatnam, Andhra Pradesh (India). Strain N9T was found to be positive for oxidase and catalase activities. The fatty acids were found to be dominated by C16:0, C18:1 ω7c and summed in feature 3 (C16:1 ω7c and/or C16:1 ω6c). Strain N9T was determined to contain Q-10 as the major respiratory quinone and phosphatidylethanolamine, phosphatidylglycerol, two aminophospholipids, two phospholipids and four unidentified lipids as polar lipids. The DNA G+C content of the strain N9T was found to be 63 mol%. 16S rRNA gene sequence analysis indicated that Rhodobacter sphaeroides, Rhodobacter johrii, Pseudorhodobacter ferrugineus, Rhodobacter azotoformans, Rhodobacter ovatus and Pseudorhodobacter aquimaris were the nearest phylogenetic neighbours, with pair-wise sequence similarities of 95.43, 95.36, 94.24, 95.31, 95.60 and 94.74 %, respectively. Phylogenetic analysis showed that strain N9T formed a distinct branch within the family Rhodobacteraceae and clustered with the clade comprising species of the genus Pseudorhodobacter, together with species of the genera Roseicitreum, Roseinatronobacter, Roseibaca and Rhodobaca. Species of the genus Pseudorhodobacter are phylogenetically close with a 16S rRNA gene sequence dissimilarity of 5.9–7.3 % (92.7–94.1 % similarity). Based on the above-mentioned phenotypic characteristics and on phylogenetic inference, strain N9T is proposed as a representative of a new genus and a novel species of the family Rhodobacteraceae as Albirhodobacter marinus gen. nov., sp. nov. The type strain of Albirhodobacter marinus is N9 (= MTCC 11277T = JCM 17680T). 相似文献
50.
Chandrasekhar Chanda Angshuman Sarkar Srinivas Sistla Dibakar Chakrabarty 《Biochemical and biophysical research communications》2013
A low molecular weight anti-platelet peptide (6.9 kDa) has been purified from Naja kaouthia venom and was named KT-6.9. MALDI-TOF/TOF mass spectrometry analysis revealed the homology of KT-6.9 peptide sequence with many three finger toxin family members. KT-6.9 inhibited human platelet aggregation process in a dose dependent manner. It has inhibited ADP, thrombin and arachidonic acid induced platelet aggregation process in dose dependent manner, but did not inhibit collagen and ristocetin induced platelet aggregation. Strong inhibition (70%) of the ADP induced platelet aggregation by KT-6.9 suggests competition with ADP for its receptors on platelet surface. Anti-platelet activity of KT-6.9 was found to be 25 times stronger than that of anti-platelet drug clopidogrel. Binding of KT-6.9 to platelet surface was confirmed by surface plasma resonance analysis using BIAcore X100. Binding was also observed by a modified sandwich ELISA method using anti-KT-6.9 antibodies. KT-6.9 is probably the first 3FTx from Indian monocled cobra venom reported as a platelet aggregation inhibitor. 相似文献