全文获取类型
收费全文 | 797篇 |
免费 | 31篇 |
国内免费 | 3篇 |
专业分类
831篇 |
出版年
2023年 | 4篇 |
2022年 | 22篇 |
2021年 | 33篇 |
2020年 | 14篇 |
2019年 | 14篇 |
2018年 | 24篇 |
2017年 | 19篇 |
2016年 | 27篇 |
2015年 | 19篇 |
2014年 | 31篇 |
2013年 | 74篇 |
2012年 | 46篇 |
2011年 | 51篇 |
2010年 | 39篇 |
2009年 | 32篇 |
2008年 | 47篇 |
2007年 | 41篇 |
2006年 | 54篇 |
2005年 | 30篇 |
2004年 | 30篇 |
2003年 | 32篇 |
2002年 | 26篇 |
2001年 | 15篇 |
2000年 | 6篇 |
1999年 | 6篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1985年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1974年 | 2篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1962年 | 2篇 |
排序方式: 共有831条查询结果,搜索用时 15 毫秒
61.
Fatthalla MI Elkholy YM Abbas NS Mandour AH Jørgensen PT Bomholt N Pedersen EB 《Bioorganic & medicinal chemistry》2012,20(1):207-214
A new intercalating nucleic acid monomer M comprising a 4-(1-indole)-butane-1,2-diol moiety was synthesized via a classical alkylation reaction of indole-3-carboxaldehyde followed by a condensation reaction with phenanthrene-9,10-dione in the presence of ammonium acetate to form a phenanthroimidazole moiety linked to the indole ring. Insertion of the new intercalator as a bulge into a Triplex Forming Oligonucleotide resulted in good thermal stability of the corresponding Hoogsteen-type triplexes. Molecular modeling supports the possible intercalating ability of M. Hybridisation properties of DNA/DNA and RNA/DNA three-way junctions (TWJ) with M in the branching point were also evaluated by their thermal stability at pH 7. DNA/DNA TWJ showed increase in thermal stability compared to wild type oligonucleotides whereas this was not the case for RNA/DNA TWJ. 相似文献
62.
Age-related cataract is clinically and genetically heterogeneous disorder affecting the ocular lens, and the leading cause of vision loss and blindness worldwide. Here we screened nonsynonymous single nucleotide polymorphisms (nsSNPs) of a novel gene, EPHA2 responsible for age related cataracts. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on protein was predicted by PolyPhen and SIFT respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the EPHA2 protein was evaluated by using SWISSPDB viewer and NOMAD-Ref server. Our analysis revealed 16 SNPs as nonsynonymous out of which 6 nsSNPs, namely rs11543934, rs2291806, rs1058371, rs1058370, rs79100278 and rs113882203 were found to be least stable by I-Mutant 2.0 with DDG value of > -1.0. nsSNPs, namely rs35903225, rs2291806, rs1058372, rs1058370, rs79100278 and rs113882203 showed a highly deleterious tolerance index score of 0.00 by SIFT server. Four nsSNPs namely rs11543934, rs2291806, rs1058370 and rs113882203 were found to be probably damaging with PSIC score of ≥ 2. 0 by Polyp hen server. Three nsSNPs namely, rs11543934, rs2291806 and rs1058370 were found to be highly polymorphic with a risk score of 3-4 with a possible effect of Non-conservative change and splicing regulation by FASTSNP. The total energy and RMSD value was higher for the mutant-type structure compared to the native type structure. We concluded that the nsSNP namely rs2291806 as the potential functional polymorphic that is likely to have functional impact on the EPHA2 gene. 相似文献
63.
Oritavancin exhibits dual mode of action to inhibit cell-wall biosynthesis in Staphylococcus aureus 总被引:1,自引:0,他引:1
Kim SJ Cegelski L Stueber D Singh M Dietrich E Tanaka KS Parr TR Far AR Schaefer J 《Journal of molecular biology》2008,377(1):281-293
Solid-state NMR measurements performed on intact whole cells of Staphylococcus aureus labeled selectively in vivo have established that des-N-methylleucyl oritavancin (which has antimicrobial activity) binds to the cell-wall peptidoglycan, even though removal of the terminal N-methylleucyl residue destroys the d-Ala-d-Ala binding pocket. By contrast, the des-N-methylleucyl form of vancomycin (which has no antimicrobial activity) does not bind to the cell wall. Solid-state NMR has also determined that oritavancin and vancomycin are comparable inhibitors of transglycosylation, but that oritavancin is a more potent inhibitor of transpeptidation. This combination of effects on cell-wall binding and biosynthesis is interpreted in terms of a recent proposal that oritavancin-like glycopeptides have two cell-wall binding sites: the well-known peptidoglycan d-Ala-d-Ala pentapeptide stem terminus and the pentaglycyl bridging segment. The resulting dual mode of action provides a structural framework for coordinated cell-wall assembly that accounts for the enhanced potency of oritavancin and oritavancin-like analogues against vancomycin-resistant organisms. 相似文献
64.
Mounawer Badri Adel Zitoun Sameh Soula Houcine Ilahi Thierry Huguet Mohamed Elarbi Aouani 《Conservation Genetics》2008,9(6):1509-1520
In this paper, we analyze the genetic variability in four Tunisian natural populations of Medicago ciliaris using 19 quantitative traits and six polymorphic microsatellite loci. We investigated the amplification transferability of
30 microsatellites developed in the model legume M. truncatula to M. ciliaris. Results revealed that about 56.66% of analyzed markers are valuable genetic markers for M. ciliaris. The most genetic diversity at quantitative traits and microsatellite loci was found to occur within populations (>80%).
Low differentiations among populations at quantitative traits Q
ST
= 0.146 and molecular markers F
ST
= 0.18 were found. The majority of measured traits exhibited no significant difference in the level of Q
ST
and F
ST
. Furthermore, significant correlations established between these traits and eco-geographical factors suggested that natural
selection should be invoked to explain the level of phenotypic divergence among populations rather than drift. There was no
significant correlation between population differentiation at quantitative traits and molecular markers. Significant spatial
genetic structure consistent with models of isolation by distance was detected within all studied populations. The site-of-origin
environmental factors explain about 9.07% of total phenotypic genetic variation among populations. The eco-geographical factors
that influence more the variation of measured traits among populations are the soil texture and altitude. Nevertheless, there
were no consistent pattern of associations between gene diversity (He) and environmental factors. 相似文献
65.
66.
Li H Zhou J Miki J Furusato B Gu Y Srivastava S McLeod DG Vogel JC Rhim JS 《Experimental cell research》2008,314(1):92-102
Understanding prostate stem cells may provide insight into the origin of prostate cancer. Primary cells have been cultured from human prostate tissue but they usually survive only 15-20 population doublings before undergoing senescence. We report here that RC-170N/h/clone 7 cells, a clonal cell line from hTERT-immortalized primary non-malignant tissue-derived human prostate epithelial cell line (RC170N/h), retain multipotent stem cell properties. The RC-170N/h/clone 7 cells expressed a human embryonic stem cell marker, Oct-4, and potential prostate epithelial stem cell markers, CD133, integrin alpha2beta1(hi) and CD44. The RC-170N/h/clone 7 cells proliferated in KGM and Dulbecco's Modified Eagle Medium with 10% fetal bovine serum and 5 microg/ml insulin (DMEM+10% FBS+Ins.) medium, and differentiated into epithelial stem cells that expressed epithelial cell markers, including CK5/14, CD44, p63 and cytokeratin 18 (CK18); as well as the mesenchymal cell markers, vimentin, desmin; the neuron and neuroendocrine cell marker, chromogranin A. Furthermore the RC170 N/h/clone 7 cells differentiated into multi tissues when transplanted into the sub-renal capsule and subcutaneously of NOD-SCID mice. The results indicate that RC170N/h/clone 7 cells retain the properties of multipotent stem cells and will be useful as a novel cell model for studying the mechanisms of human prostate stem cell differentiation and transformation. 相似文献
67.
Robert W. Evans Roozina Rafique Adel Zarea Chiara Rapisarda Richard Cammack Patricia J. Evans John B. Porter Robert C. Hider 《Journal of biological inorganic chemistry》2008,13(1):57-74
Despite its importance in iron-overload diseases, little is known about the composition of plasma non-transferrin-bound iron
(NTBI). Using 30-kDa ultrafiltration, plasma from thalassemic patients consisted of both filterable and non-filterable NTBI,
the filterable fraction representing less than 10% NTBI. Low filterability could result from protein binding or NTBI species
exceeding 30 kDa. The properties of iron citrate and its interaction with albumin were therefore investigated, as these represent
likely NTBI species. Iron permeated 5- or 12-kDa ultrafiltration units completely when complexes were freshly prepared and
citrate exceeded iron by tenfold, whereas with 30-kDa ultrafiltration units, permeation approached 100% at all molar ratios.
A g = 4.3 electron paramagnetic resonance signal, characteristic of mononuclear iron, was detectable only with iron-to-citrate
ratios above 1:100. The ability of both desferrioxamine and 1,2-dimethyl-3-hydroxypyridin-4-one to chelate iron in iron citrate
complexes also increased with increasing ratios of citrate to iron. Incremental molar excesses of citrate thus favour the
progressive appearance of chelatable lower molecular weight iron oligomers, dimers and ultimately monomers. Filtration of
iron citrate in the presence of albumin showed substantial binding to albumin across a wide range of iron-to-citrate ratios
and also increased accessibility of iron to chelators, reflecting a shift towards smaller oligomeric species. However, in
vitro experiments using immunodepletion or absorption of albumin to Cibacron blue–Sepharose indicate that iron is only loosely
bound in iron citrate–albumin complexes and that NTBI is unlikely to be albumin-bound to any significant extent in thalassemic
sera. 相似文献
68.
69.
Mohammed Ramdani Roger J. Flower Najat Elkhiati with contributions from Hilary H. Birks Mohammed M. Kraïem Adel A. Fathi 《Aquatic Ecology》2001,35(3-4):389-403
Palaeolimnological studies were carried out on sediment cores from nine North African wetland lakes. The lakes represented a variety of habitats ranging from freshwater to mixohaline conditions and with and without direct connections to the sea. Sediment cores were examined for records of recent environmental change during the 20th century period. Faunal remains analysed in the sediments included those of Cladocera, Ostracoda, Chironomidae, Mollusca and, at the sites with marine connections, Foraminifera.
Cyprideis
torosa littoralis was the most common ostracod, occurring in sediments from the seven sites linked with the sea and also in brackish water Sidi Bou Rhaba. In acid Megene Chitane ostracods were scarce, being represented by a single species (Cypria ophtalmica).
Candona neglecta completely disappeared at two sites (Sidi Bou Rhaba and Bokka) during the 20th century. Of the Cladocera, Chydorus sphaericus was common in the moderately mixohaline sites and but Heterocypris salina occurred only where marine salinities were occasionally achieved (in Zerga, Ichkeul and Korba). Microinvertebrate assemblages in the Nile Delta lake cores and to a less extent in Zerga showed a clear response indicative of more fresher conditions occurring during the latter part of the 20th century. However the freshening trend began prior to construction of the Aswan High Dam (mid 1960s).With the exception of the most saline site (Korba), microinvertebrate communiuties at all the CASSARINA sites have experienced major disturbances during the 20th century. Changes in freshwater availability associated with increased human usage of water resources is perceived as a major factor regulating the abundance and occurrence of aquatic microinvertebrate species at these sites 相似文献
70.
El-Faham Ayman El Massry Abdel Moneim Amer Adel Gohar Yousry M. 《International journal of peptide research and therapeutics》2002,9(1):49-54
Summary The synthesis ofN-protected L-amino acid (3-benzylquinoxalin-2-yl) hydrazide derivatives is reported here. 3-Benzyl-2-hydrazinoquinoxaline
was prepared and then coupled withN-Boc-L-amino acids including; Alanine, Valine, Leucine, Phenylalanine, Tyrosine, Serine and Proline in the presence of HBTU
as a coupling reagent to provide the expected product with high yield and purity. The products were deprotected by p-toluenesulphonic
acid in acetonitrile and then the tosylate salts were evaluated for antibacterial and antifungal activity.
Abbreviations: HBTU, N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium hexafluorophosphate N-oxide Boc,t-butyloxycarbonyl, DIEA, diisopropylethylamine; DMF, N,N-dimethylformamide; PTSA, p-toluenesulphonic acid, TEA, triethyl amine.
Amino acids are abbreviated and designated following the rules of the IUPAC-IUB Commission of BiochemicalNomenclature (J. Biol. Chem., 247 (1972) 977). 相似文献