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31.
32.
Aditya Nath Jha Vipin Kumar Singh Namrata Kumari Ashish Singh Justin Antony Hoang van Tong Sakshi Singh Sudhanshu S. Pati Pradeep K. Patra Rajender Singh Nguyen L. Toan Le H. Song Amal Assaf Iara J. T. Messias–Reason Thirumalaisamy P. Velavan Lalji Singh Kumarasamy Thangaraj 《PloS one》2012,7(10)
Background
Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between TH1 and TH2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.Methods
We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).Results
The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r2>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 –0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ2 3 = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).Conclusions
Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection. 相似文献33.
The purpose of this research was to mask the intensely bitter taste of primaquine phosphate (PRM) and to formulate suspension
powder (cachets) of the taste masked drug. Taste masking was done using beta-cyclodextrin. To characterize and formulate taste
masked cachets of PRM, the 1:25 M physical mixture was selected based on bitterness score. Phase solubility studies, fourier
transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD) were
performed to identify the physicochemical interaction between drug and carrier, hence its effect on dissolution. Cachets were
evaluated for angle of repose, sedimentation characterization and pH. In vitro drug release studies for physical mixture and kneaded system were performed at pH, 1.2 and 6.8. Bitterness score was evaluated
using gustatory sensation test. Phase solubility studies showed weak interaction between PRM and CD. The FTIR, DSC and XRPD
studies indicated inclusion complexation in physical mixture and kneaded system. In addition, kneaded system and physical
mixture exhibited better drug release at pH 1.2 and negligible effect at pH 6.8. Cachets prepared using physical mixture,
(DS24), showed complete bitter taste masking and easy redispersibility. Taste evaluation of cachets in human volunteers rated
tasteless with a score of 0 to DS24 and 3 to DS25. Thus, results conclusively demonstrated successful taste masking and formulation
of cachets with taste masked drug. 相似文献
34.
The genome sequence of the cyanobacterium Synechocystis sp. PCC6803 revealed four Open reading frame (ORF) encoding putative inositol monophosphatase or inositol monophosphatase-like
proteins. One of the ORFs, sll1383, is ∼870 base pair long and has been assigned as a probable myo-inositol 1 (or 4) monophosphatase (IMPase; EC 3.1.3.25). IMPase is the second enzyme in the inositol biosynthesis pathway
and catalyses the conversion of L-myo-inositol 1-phosphate to free myo-inositol. The present work describes the functional assignment of ORF sll1383 as myo-inositol 1-phosphate phosphatase (IMPase) through molecular cloning, bacterial overexpression, purification and biochemical
characterization of the gene product. Affinity (K
m) of the recombinant protein for the substrate DL-myo-inositol 1-phosphate was found to be much higher (0.0034 ± 0.0003 mM) compared to IMPase(s) from other sources but in comparison
V
max (∼0.033 μmol Pi/min/mg protein) was low. Li+ was found to be an inhibitor (IC50 6.0 mM) of this enzyme, other monovalent metal ions (e.g. Na+, K+ NH4+) having no significant effect on the enzyme activity. Like other IMPase(s), the activity of this enzyme was found to be totally
Mg2+ dependent, which can be substituted partially by Mn2+. However, unlike other IMPase(s), the enzyme is optimally active at ∼42°C. To the best of our knowledge, sll1383 encoded
IMPase has the highest substrate affinity and specificity amongst the known examples from other prokaryotic sources. A possible
application of this recombinant protein in the enzymatic coupled assay of L-myo-inositol 1-phosphate synthase (MIPS) is discussed. 相似文献
35.
Ghosh Chiranjit Patra Debashis Bala Niranjan Majumder Indira Sepay Nayim Mukhopadhyay Prabuddha Das Sukhen Kundu Rita Drew Michael G. B. León Armando Rafael Ghosh Tapas Pradhan Manik 《Biometals》2022,35(3):499-517
BioMetals - A family of dioxidovanadium(V) complexes (1–4) of the type [Na(H2O)x]+[VVO2(HL1?4)]? (x?=?4, 4.5 and 7) where HL2? represents the dianionic form of... 相似文献
36.
Amritaj Patra Qianqian Zhang Li Lei Yan Su Martin Egli F. Peter Guengerich 《The Journal of biological chemistry》2015,290(13):8028-8038
The most common lesion in DNA is an abasic site resulting from glycolytic cleavage of a base. In a number of cellular studies, abasic sites preferentially code for dATP insertion (the “A rule”). In some cases frameshifts are also common. X-ray structures with abasic sites in oligonucleotides have been reported for several microbial and human DNA polymerases (pols), e.g. Dpo4, RB69, KlenTaq, yeast pol ι, human (h) pol ι, and human pol β. We reported previously that hpol η is a major pol involved in abasic site bypass (Choi, J.-Y., Lim, S., Kim, E. J., Jo, A., and Guengerich, F. P. (2010 J. Mol. Biol. 404, 34–44). hpol η inserted all four dNTPs in steady-state and pre-steady-state assays, preferentially inserting A and G. In LC-MS analysis of primer-template pairs, A and G were inserted but little C or T was inserted. Frameshifts were observed when an appropriate pyrimidine was positioned 5′ to the abasic site in the template. In x-ray structures of hpol η with a non-hydrolyzable analog of dATP or dGTP opposite an abasic site, H-bonding was observed between the phosphate 5′ to the abasic site and water H-bonded to N1 and N6 of A and N1 and O6 of G nucleoside triphosphate analogs, offering an explanation for what appears to be a “purine rule.” A structure was also obtained for an A inserted and bonded in the primer opposite the abasic site, but it did not pair with a 5′ T in the template. We conclude that hpol η, a major copying enzyme with abasic sites, follows a purine rule, which can also lead to frameshifts. The phenomenon can be explained with H-bonds. 相似文献
37.
Patra Falguni Tomar Sudhir Kumar Rajput Yudhishthir Singh Singh Rameshwar 《World journal of microbiology & biotechnology》2011,27(4):933-939
Mannitol is a naturally occurring low calorie sweetener, widely used in the food, pharmaceutical, medicine and chemical industries.
In this study mannitol producing strains of Leuconostoc spp. (210) were isolated from a wide array of sources such as raw milk, fermented milks, fermented cereal foods, fruits,
vegetables and sugar factory syrup. During initial screening, half of the population of these isolates (105) exhibited ability
to produce mannitol to a variable extent. Only 11.4% isolate produced mannitol yield of above 80% (when fructose used @ 50 g/l).
Cultural and environmental factors affecting growth and mannitol production were studied for four high mannitol producing
isolates. High mannitol production was favored by high temperature and high pH. Isolates had high osmotic tolerance as these
could use fructose concentration as high as 100 g/l in batch culture. Sequencing of 16S rRNA genes of the strains revealed
that Ln27, Ln104 and Ln206 were Leuconostoc mesenteroides and Ln92 was Leuconostoc fallax. 相似文献
38.
Chakravorty D Parameswaran S Dubey VK Patra S 《Extremophiles : life under extreme conditions》2011,15(1):89-103
Thermostable lipases are of high priority for industrial applications as they are endowed with the capability of carrying
out diversified reactions at elevated temperatures. Extremophiles are their potential source. Sequence and structure annotation
of thermostable lipases can elucidate evolution of lipases from their mesophilic counterparts with enhanced thermostability
hence better industrial potential. Sequence analysis highlighted the conserved residues in bacterial and fungal thermostable
lipases. Higher frequency of AXXXA motif and poly Ala residues in lid domain of thermostable Bacillus lipases were distinguishing characteristics. Comparison of amino acid composition among thermostable and mesostable lipases
brought into light the role of neutral, charged and aromatic amino acid residues in enhancement of thermostability. Structural
annotation of thermostable lipases with that of mesostable lipases revealed some striking features which are increment of
gamma turns in thermostable lipases; being first time reported in our paper, longer beta strands, lesser beta-branched residues
in helices, increase in charged-neutral hydrogen bonding pair, hydrophobic-hydrophobic contact and differences in the N-cap
and C-cap residues of the α helices. Conclusively, it can be stated that subtle changes in the arrangement of amino acid residues
in the tertiary structure of lipases contributes to enhanced thermostability. 相似文献
39.
Around 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60% in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers. Despite its clinical success, critical challenges like resistance, off-target side effects and cancer variability often reduce its overall therapeutic efficiency. These challenges require faster diagnosis, simultaneous therapy and a more personalized approach toward cancer management. To this end, small-molecule ‘theranostic’ agents have presented a viable solution combining diagnosis and therapy into a single platform. In this review, we present a summary of recent efforts in the design and optimization of metal-based small-molecule ‘theranostic’ anticancer agents. Importantly, we highlight the advantages of a theranostic candidate over the purely therapeutic or diagnostic agent in terms of evaluation of its biological properties. 相似文献
40.
Duncan JG Ravi R Stull LB Murphy AM 《American journal of physiology. Heart and circulatory physiology》2005,289(4):H1512-H1518
Heart failure is a clinical syndrome associated with elevated levels of oxygen-derived free radicals. Xanthine oxidase activity is believed to be one source of reactive oxygen species in the failing heart. Interventions designed to reduce oxidative stress are believed to have significant therapeutic potential in heart failure. This study tested the hypothesis that xanthine oxidase activity would be elevated in a mouse model of dilated cardiomyopathy and evaluated the effect of chronic oral allopurinol, an inhibitor of xanthine oxidase, on contractility and progressive ventricular dilation in these mice. Nontransgenic and transgenic mice containing a troponin I truncation were treated with oral allopurinol from 2-4 mo of age. Myocardial xanthine oxidase activity was threefold higher in untreated transgenic mice compared with nontransgenic mice. Analyses of myofilament proteins for modification of carbonyl groups demonstrated myofibrillar protein damage in untreated transgenic mice. Treatment with allopurinol for 2 mo suppressed xanthine oxidase activity and myofibrillar protein oxidation. Allopurinol treatment also alleviated ventricular dilation and preserved shortening fraction in the transgenic animals. In addition, cardiac muscle twitch tension was preserved to 70% of nontransgenic levels in allopurinol-treated transgenic mice, a significant improvement over untreated transgenic mice. These findings indicate that chronic inhibition of xanthine oxidase can alter the progression of heart failure in dilated cardiomyopathy. 相似文献