全文获取类型
收费全文 | 2015篇 |
免费 | 146篇 |
国内免费 | 2篇 |
专业分类
2163篇 |
出版年
2023年 | 11篇 |
2022年 | 20篇 |
2021年 | 60篇 |
2020年 | 35篇 |
2019年 | 28篇 |
2018年 | 52篇 |
2017年 | 44篇 |
2016年 | 53篇 |
2015年 | 87篇 |
2014年 | 94篇 |
2013年 | 125篇 |
2012年 | 164篇 |
2011年 | 145篇 |
2010年 | 85篇 |
2009年 | 65篇 |
2008年 | 97篇 |
2007年 | 71篇 |
2006年 | 78篇 |
2005年 | 74篇 |
2004年 | 62篇 |
2003年 | 66篇 |
2002年 | 47篇 |
2001年 | 40篇 |
2000年 | 32篇 |
1999年 | 25篇 |
1998年 | 14篇 |
1997年 | 17篇 |
1995年 | 10篇 |
1994年 | 13篇 |
1992年 | 36篇 |
1991年 | 24篇 |
1990年 | 23篇 |
1989年 | 22篇 |
1988年 | 15篇 |
1987年 | 23篇 |
1986年 | 13篇 |
1985年 | 24篇 |
1984年 | 29篇 |
1983年 | 16篇 |
1982年 | 16篇 |
1981年 | 18篇 |
1979年 | 24篇 |
1978年 | 14篇 |
1977年 | 13篇 |
1975年 | 12篇 |
1974年 | 14篇 |
1973年 | 10篇 |
1969年 | 13篇 |
1968年 | 10篇 |
1966年 | 10篇 |
排序方式: 共有2163条查询结果,搜索用时 0 毫秒
61.
62.
63.
Santosh George Bruno Levecke Deepthi Kattula Vasanthakumar Velusamy Sheela Roy Peter Geldhof Rajiv Sarkar Gagandeep Kang 《PLoS neglected tropical diseases》2016,10(8)
BackgroundHookworms (Necator americanus and Ancylostoma duodenale) remain a major public health problem worldwide. Infections with hookworms (e.g., A. caninum, A. ceylanicum and A. braziliense) are also prevalent in dogs, but the role of dogs as a reservoir for zoonotic hookworm infections in humans needs to be further explored.Conclusions/SignificanceIn our study we regularly detected the presence of A. caninum DNA in the stool of humans. Whether this is the result of infection is currently unknown but it does warrant a closer look at dogs as a potential reservoir. 相似文献
64.
Kamlesh K. Meena Manish Kumar Snehasish Mishra Sanjay Kumar Ojha Goraksha C. Wakchaure Biplab Sarkar 《Indian journal of microbiology》2015,55(2):151-162
Group-wise diversity of sediment methylotrophs of Chilika lake (Lat. 19°28′–19°54′N; Long. 85°06′–85°35′E) Odisha, India at various identified sites was studied. Both the culturable and unculturable (metagenome) methylotrophs were investigated in the lake sediments employing both mxaF and 16S rRNA genes as markers. ARDRA profiling, 16S rRNA gene sequencing, PAGE profiling of HaeIII, EcoRI restricted mxaF gene and the mxaF gene sequences using culture-dependent approach revealed the relatedness of α-proteobacteria and Methylobacterium, Hyphomicrobium and Ancyclobacter sp. The total viable counts of the culturable aerobic methylotrophs were relatively higher in sediments near the sea mouth (S3; Panaspada), also demonstrated relatively high salinity (0.1 M NaCl) tolerance. Metagenomic DNA from the sediments, amplified using GC clamp mxaF primers and resolved through DGGE, revealed the diversity within the unculturable methylotrophic bacterium Methylobacterium organophilum, Ancyclobacter aquaticus, Burkholderiales and Hyphomicrobium sp. Culture-independent analyses revealed that up to 90 % of the methylotrophs were unculturable. The study enhances the general understandings of the metagenomic methylotrophs from such a special ecological niche.
Electronic supplementary material
The online version of this article (doi:10.1007/s12088-015-0510-3) contains supplementary material, which is available to authorized users. 相似文献65.
Anindita Sarkar 《Inorganica chimica acta》2009,362(10):3807-1603
In acetonitrile, reactions of bis(acetylacetonato)oxidovanadium(IV) ([VO(acac)2]) with 4-R-benzoylhydrazine in 1:1 mole ratio provide coordinatively symmetrical complexes (1-5) of the {OV(μ-O)VO}4+ motif in 40-47% yields. On the other hand, in methanol the same reactants provide complexes (6-10) containing the {OV(μ-OMe)2VO}4+ core in 37-50% yields. In both series of complexes, the ligand is the O,N,O-donor deprotonated Schiff base system 4-R-benzoic acid (1-methyl-3-oxo-butylidene)-hydrazide formed by template condensation of acac− with 4-R-benzoylhydrazine (R = H, Cl, OMe, NO2 and NMe2). All the complexes have been characterized by elemental analysis, magnetic and spectroscopic (IR, UV-Vis and NMR) measurements. Molecular structures of three representative complexes (4, 6 and 7) have been determined by X-ray crystallography. In each complex, the dianionic planar ligand is coordinated to the metal centre via the enolate-O, the imine-N and the O-atom of the deprotonated amide functionality. Cyclic voltammetric measurements in dichloromethane revealed that complexes 1-5 are redox inactive, while complexes 6-10 display a metal centred reduction in the potential range −0.06 to 0.0.32 V (versus Ag/AgCl). 相似文献
66.
Sarkar G Curran GL Mahlum E Decklever T Wengenack TM Blahnik A Hoesley B Lowe VJ Poduslo JF Jenkins RB 《PloS one》2011,6(12):e28881
Background
Therapeutic intervention of numerous brain-associated disorders currently remains unrealized due to serious limitations imposed by the blood-brain-barrier (BBB). The BBB generally allows transport of small molecules, typically <600 daltons with high octanol/water partition coefficients, but denies passage to most larger molecules. However, some receptors present on the BBB allow passage of cognate proteins to the brain. Utilizing such receptor-ligand systems, several investigators have developed methods for delivering proteins to the brain, a critical requirement of which involves covalent linking of the target protein to a carrier entity. Such covalent modifications involve extensive preparative and post-preparative chemistry that poses daunting limitations in the context of delivery to any organ. Here, we report creation of a 36-amino acid peptide transporter, which can transport a protein to the brain after routine intravenous injection of the transporter-protein mixture. No covalent linkage of the protein with the transporter is necessary.Approach
A peptide transporter comprising sixteen lysine residues and 20 amino acids corresponding to the LDLR-binding domain of apolipoprotein E (ApoE) was synthesized. Transport of beta-galactosidase, IgG, IgM, and antibodies against amyloid plques to the brain upon iv injection of the protein-transporter mixture was evaluated through staining for enzyme activity or micro single photon emission tomography (micro-SPECT) or immunostaining. Effect of the transporter on the integrity of the BBB was also investigated.Principal Findings
The transporter enabled delivery to the mouse brain of functional beta-galactosidase, human IgG and IgM, and two antibodies that labeled brain-associated amyloid beta plaques in a mouse model of Alzheimer''s disease.Significance
The results suggest the transporter is able to transport most or all proteins to the brain without the need for chemically linking the transporter to a protein. Thus, the approach offers an avenue for rapid clinical evaluation of numerous candidate drugs against neurological diseases including cancer. (299 words). 相似文献67.
A proximo-distal gradient of reduced glutathione (GSH), a non enzymatic antioxidant was observed in the original tails of the lizard, H. leschenaultii. In the regenerating tails, a gradual increase in the level of GSH was noted with tail elongation. In the newly regenerated tails also the level of GSH remained higher in the proximal part than the corresponding distal parts. 相似文献
68.
Scott Pownall Christine A. Kozak Keith Schappert Mohan Sarkar Eric Hull Harry Schachter Jamey D. Marth 《Genomics》1992,12(4)
The biosynthesis of protein-bound complex N-glycans in mammals requires a series of covalent modifications governed by a large number of specific glycosyltransferases and glycosidases. The addition of oligosaccharide to an asparagine residue on a nascent polypeptide chain begins in the endoplasmic reticulum. Oligosaccharide processing continues in the Golgi apparatus to produce a diversity of glycan structures. UDP-N-acetylglucosamine:α-3-
-mannoside β-1,2-N-acetylglucosaminyltransferase I (EC 2.4.1.101; GlcNAc-TI) is a key enzyme in the process because it is essential for the conversion of high-mannose N-glycans to complex and hybrid N-glycans. We have isolated the mouse gene encoding GlcNAc-TI (Mgat-1) from a genomic DNA library. The mouse sequence is highly conserved with respect to the human and rabbit homologs and exists as a single protein-encoding exon. Mgat-1 was mapped to mouse Chromosome 11, closely linked to the gene encoding interleukin-3 by the analysis of multilocus interspecies backcrosses. RNA analyses of Mgat-1 expression levels revealed significant variation among normal tissues and cells. 相似文献
69.
Putative Virulence Traits and Pathogenicity of Vibrio cholerae Non-O1, Non-O139 Isolates from Surface Waters in Kolkata, India 下载免费PDF全文
Prasanta K. Bag Poulami Bhowmik Tapas K. Hajra T. Ramamurthy Pradipta Sarkar Mrinmoyee Majumder Goutam Chowdhury Suresh C. Das 《Applied microbiology》2008,74(18):5635-5644
Vibrio cholerae non-O1, non-O139 was isolated from natural surface waters from different sites sampled in diarrhea endemic zones in Kolkata, India. Twenty-one of these isolates were randomly selected and included in the characterization. The multiserogroup isolates were compared by their virulence traits with a group of clinical non-O1, non-O139 isolates from the same geographic area. Of the 21 environmental isolates, 6 and 14 strains belonged to Heiberg groups I and II, respectively. Three of the environmental isolates showed resistance to 2,2-diamine-6,7-diisopropylpteridine phosphate. All of the non-O1, non-O139 strains were positive for toxR, and except for one environmental isolate, none of them were positive for tcpA in the PCR assay. None of the isolates were positive for genes encoding cholera toxin (ctxA), heat-stable toxin (est), heat-labile toxin (elt), and Shiga toxin variants (stx) of Escherichia coli. Additionally, except for one environmental isolate (PC32), all were positive for the gene encoding El Tor hemolysin (hly). The culture supernatants of 86% (18 of 21) of the environmental isolates showed a distinct cytotoxic effect on HeLa cells, and some of these strains also produced cell-rounding factor. The lipase, protease, and cell-associated hemagglutination activities and serum resistance properties of the environmental and clinical isolates did not differ much. However, seven environmental isolates exhibited very high hemolytic activities (80 to 100%), while none of the clinical strains belonged to this group. The environmental isolates manifested three adherence patterns, namely, carpet-like, diffuse, and aggregative adherence, and the clinical isolates showed diffuse adherence on HeLa cells. Of the 11 environmental isolates tested for enteropathogenic potential, 8 (73%) induced positive fluid accumulation (≥100) in a mouse model, and the reactivities of these isolates were comparable to those of clinical strains of non-O1, non-O139 and toxigenic O139 V. cholerae. Comparison of the counts of the colonized environmental and clinical strains in the mouse intestine showed that the organisms of both groups had similar colonizing efficiencies. These findings indicate the presence of potentially pathogenic V. cholerae non-O1, non-O139 strains in surface waters of the studied sites in Kolkata. 相似文献
70.
Interactions of bisANS and ANS to tubulin in the presence and absence of GTP were investigated, and the binding and thermodynamic parameters were determined using isothermal titration calorimetry. Like bisANS binding to tubulin, we observed a large number of lower affinity ANS binding sites (N1 = 1.3, K1 = 3.7 x 10(5) M(-1), N2 = 10.5, K2 = 7 x 10(4)/M(-1)) in addition to 1-2 higher affinity sites. Although the presence of GTP lowers the bisANS binding to both higher and lower affinity sites (N1 = 4.3, N2 = 11.7 in absence and N1 = 1.8, N2 = 3.6 in presence of GTP), the stoichiometries of both higher and lower affinity sites of ANS remain unaffected in the presence of GTP. BisANS-induced structural changes on tubulin were studied using site-specific proteolysis with trypsin and chymotrypsin. Digestion of both alpha and beta tubulin with trypsin and chymotrypsin, respectively, has been found to be very specific in presence of GTP. GTP has dramatic effects on lowering the extent of nonspecific digestion of beta tubulin with trypsin and stabilizing the intermediate bands produced from both alpha and beta. BisANS-treated tubulin is more susceptible to both trypsin and chymotrypsin digestion. At higher bisANS concentration (>20 microM) both alpha and beta tubulins are almost totally digested with enzymes, indicating bisANS-induced unfolding or destabilization of tubulin structure. Again, the addition of GTP has remarkable effect on lowering the bisANS-induced enhanced digestion of tubulin as well as stabilizing effect on intermediate bands. These results of isothermal titration calorimetry, proteolysis and the DTNB-kinetics data clearly established that the addition of GTP makes tubulin compact and rigid and hence the GTP-induced stabilization of tubulin structure. No such destabilization of tubulin structure has been noticed with ANS, although, like bisANS, ANS possesses a large number of lower affinity binding sites. On the basis of these results, we propose that the unique structure of bisANS, which in absence of GTP can bind tubulin as a bifunctional ligand (through its two ANS moieties), is responsible for the structural changes of tubulin. 相似文献