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21.
Background
Despite the remarkable progress of bioinformatics, how the primary structure of a protein leads to a three-dimensional fold, and in turn determines its function remains an elusive question. Alignments of sequences with known function can be used to identify proteins with the same or similar function with high success. However, identification of function-related and structure-related amino acid positions is only possible after a detailed study of every protein. Folding pattern diversity seems to be much narrower than sequence diversity, and the amino acid sequences of natural proteins have evolved under a selective pressure comprising structural and functional requirements acting in parallel.Principal Findings
The approach described in this work begins by generating a large number of amino acid sequences using ROSETTA [Dantas G et al. (2003) J Mol Biol 332:449–460], a program with notable robustness in the assignment of amino acids to a known three-dimensional structure. The resulting sequence-sets showed no conservation of amino acids at active sites, or protein-protein interfaces. Hidden Markov models built from the resulting sequence sets were used to search sequence databases. Surprisingly, the models retrieved from the database sequences belonged to proteins with the same or a very similar function. Given an appropriate cutoff, the rate of false positives was zero. According to our results, this protocol, here referred to as Rd.HMM, detects fine structural details on the folding patterns, that seem to be tightly linked to the fitness of a structural framework for a specific biological function.Conclusion
Because the sequence of the native protein used to create the Rd.HMM model was always amongst the top hits, the procedure is a reliable tool to score, very accurately, the quality and appropriateness of computer-modeled 3D-structures, without the need for spectroscopy data. However, Rd.HMM is very sensitive to the conformational features of the models'' backbone. 相似文献22.
Martínez de Villarreal L Pérez JZ Vázquez PA Herrera RH Campos Mdel R López RA Ramírez JL Sánchez JM Villarreal JJ Garza MT Limón A López AG Bárcenas M García JR Domínguez AS Nuñez RH Ayala JL Martínez JG González MT Alvarez CG Castro RN 《Teratology》2002,66(5):249-256
BACKGROUND: Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated. METHODS: Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test). RESULTS: After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes. CONCLUSION: After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis. 相似文献
23.
José?Pedraza-ChaverríEmail author Diana?Barrera Perla?D?Maldonado Yolanda?I?Chirino Norma?A?Macías-Ruvalcaba Omar?N?Medina-Campos Leticia?Castro Marcos?I?Salcedo Rogelio?Hernández-Pando 《BMC clinical pharmacology》2004,4(1):5
Background
Oxidative and nitrosative stress have been involved in gentamicin-induced nephrotoxicity. The purpose of this work was to study the effect of S-allylmercaptocysteine, a garlic derived compound, on gentamicin-induced oxidative and nitrosative stress and nephrotoxicity. In addition, the in vitro reactive oxygen species scavenging properties of S-allylmercaptocysteine were studied. 相似文献24.
Urbina-Cano P Bobadilla-Morales L Ramírez-Herrera MA Corona-Rivera JR Mendoza-Magaña ML Troyo-Sanromán R Corona-Rivera A 《Journal of applied genetics》2006,47(4):377-382
Dietary polyphenolics, such as curcumin, have shown antioxidant and anti-inflammatory effects. Some antioxidants cause DNA
strand breaks in excess of transition metal ions, such as copper. The aim of this study was to evaluate thein vitro effect of curcumin in the presence of increasing concentrations of copper to induce DNA damage in murine leukocytes by the
comet assay. Balb-C mouse lymphocytes were exposed to 50 μM curcumin and various concentrations of copper (10 μM, 100 μM and
200 μM). Cellular DNA damage was detected by means of the alkaline comet assay. Our results show that 50 μM curcumin in the
presence of 100–200 μM copper induced DNA damage in murine lymphocytes. Curcumin did not inhibit the oxidative DNA damage
caused by 50 μM H2O2 in mouse lymphocytes. Moreover, 50 μM curcumin alone was capable of inducing DNA strand breaks under the tested conditions.
The increased DNA damage by 50 μM curcumin was observed in the presence of various concentrations of copper, as detected by
the alkaline comet assay. 相似文献
25.
Freitas M Da Poian AT Barth OM Rebello MA Silva JL Gaspar LP 《Cell biochemistry and biophysics》2006,44(3):325-335
Mayaro virus is an enveloped virus that belongs to the Alphavirus genus. To gain insight into the mechanism involved in Mayaro virus membrane fusion, we used hydrostatic pressure and low
pH to isolate a fusion-active state of Mayaro glycoproteins. In response to pressure, E1 glycoprotein undergoes structural
changes resulting in the formation of a stable conformation. This state was characterized and correlated to that induced by
low pH as measured by intrinsic fluorescence, 4,4′-dianilino-1,1′-binaphthyl-5,5′-disulfonic acid, dipotassium salt fluorescence,
fluorescence resonance energy transfer, electron microscopy, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis.
In parallel, we used a neutralization assay to show that Mayaro virus in the fusogenic state retained most of the original
immunogenic properties and could elicit high titers of neutralizing antibodies. 相似文献
26.
Lima LM Cordeiro Y Tinoco LW Marques AF Oliveira CL Sampath S Kodali R Choi G Foguel D Torriani I Caughey B Silva JL 《Biochemistry》2006,45(30):9180-9187
The infectious agent of transmissible spongiform encephalopathies (TSE) is believed to comprise, at least in part, the prion protein (PrP). Other molecules can modulate the conversion of the normal PrP(C) into the pathological conformer (PrP(Sc)), but the identity and mechanisms of action of the key physiological factors remain unclear. PrP can bind to nucleic acids with relatively high affinity. Here, we report small-angle X-ray scattering (SAXS) and nuclear magnetic resonance spectroscopy measurements of the tight complex of PrP with an 18 bp DNA sequence. This double-stranded DNA sequence (E2DBS) binds with nanomolar affinity to the full-length recombinant mouse PrP. The SAXS data show that formation of the rPrP-DNA complex leads to larger values of the maximum dimension and radius of gyration. In addition, the SAXS studies reveal that the globular domain of PrP participates importantly in the formation of the complex. The changes in NMR HSQC spectra were clustered in two major regions: one in the disordered portion of the PrP and the other in the globular domain. Although interaction is mediated mainly through the PrP globular domain, the unstructured region is also recruited to the complex. This visualization of the complex provides insight into how oligonucleotides bind to PrP and opens new avenues to the design of compounds against prion diseases. 相似文献
27.
Lahoucine Achnine Rogelio Pereda-Miranda Roberto Iglesias-Prieto Rafael Moreno-Sánchez Blas Lotina-Hennsen 《Physiologia plantarum》1999,106(2):246-252
Tricolorin A, (11 S )-11-hydroxyhexadecanoic acid 11- O - α - l - rhamnopyranosyl-(1↠3)- O - α - l -{2- O -(2 S -methylbutanoyl)-4- O -(2 S -methylbutanoyl)}-rhamnopyranosil-(1↠2)- O - β - d -glucopyranosil-(1↠2)- β -fucopyranoside-(1,3'-lactone), the major phytogrowth inhibitor isolated from Ipomoea tricolor Cav. (Convolvulaceae) was found to be a potent uncoupler (U50 =0.33 μ M ) of photophosphorylation in spinach chloroplasts. Tricolorin A inhibited H+ -uptake and adenosine 5'-triphosphate (ATP) synthesis, and stimulated basal and phosphorylating electron flows. Using a combination of two well-known fluorescent ΔpH probes, 9-aminoacridine and 9-amino-6-chloro-2-methoxyacridine, the uncoupling behavior of tricolorin A was also demonstrated for submitochondrial particles. Polarographic data showed that high concentrations (20 μ M ) of tricolorin A inhibited photosystem II (PSII) electron flow at the level of plastoquinone B (QB ). Chlorophyll (Chl) a fluorescence analysis showed that tricolorin A induced accumulation of QA − and strongly decreased the electron transport capacity, suggesting that the target of this molecule was located at the QB level. The macrocyclic lactone-type structure of this allelopathic agent proved to be an important structural requirement for uncoupling activity since its hydrolysis caused loss of the inhibitory potential. 相似文献
28.
Overexpression of ATP Sulfurylase in Indian Mustard Leads
to Increased Selenate Uptake, Reduction, and Tolerance 总被引:28,自引:3,他引:28
Elizabeth A.H. Pilon-Smits Seongbin Hwang C. Mel Lytle Yongliang Zhu Jenny C. Tai Rogelio C. Bravo Yichang Chen Tom Leustek Norman Terry 《Plant physiology》1999,119(1):123-132
In earlier studies, the assimilation of selenate by plants appeared to be limited by its reduction, a step that is thought to be mediated by ATP sulfurylase. Here, the Arabidopsis APS1 gene, encoding a plastidic ATP sulfurylase, was constitutively overexpressed in Indian mustard (Brassica juncea). Compared with that in untransformed plants, the ATP sulfurylase activity was 2- to 2.5-fold higher in shoots and roots of transgenic seedlings, and 1.5- to 2-fold higher in shoots but not roots of selenate-supplied mature ATP-sulfurylase-overexpressing (APS) plants. The APS plants showed increased selenate reduction: x-ray absorption spectroscopy showed that root and shoot tissues of mature APS plants contained mostly organic Se (possibly selenomethionine), whereas wild-type plants accumulated selenate. The APS plants were not able to reduce selenate when shoots were removed immediately before selenate was supplied. In addition, Se accumulation in APS plants was 2- to 3-fold higher in shoots and 1.5-fold higher in roots compared with wild-type plants, and Se tolerance was higher in both seedlings and mature APS plants. These studies show that ATP sulfurylase not only mediates selenate reduction in plants, but is also rate limiting for selenate uptake and assimilation. 相似文献
29.
Cordeiro Y Kraineva J Gomes MP Lopes MH Martins VR Lima LM Foguel D Winter R Silva JL 《Biophysical journal》2005,89(4):2667-2676
The main hypothesis for prion diseases is that the cellular protein (PrP(C)) can be altered into a misfolded, beta-sheet-rich isoform (PrP(Sc)), which undergoes aggregation and triggers the onset of transmissible spongiform encephalopathies. Here, we investigate the effects of amino-terminal deletion mutations, rPrP(Delta51-90) and rPrP(Delta32-121), on the stability and the packing properties of recombinant murine PrP. The region lacking in rPrP(Delta51-90) is involved physiologically in copper binding and the other construct lacks more amino-terminal residues (from 32 to 121). The pressure stability is dramatically reduced with decreasing N-domain length and the process is not reversible for rPrP(Delta51-90) and rPrP(Delta32-121), whereas it is completely reversible for the wild-type form. Decompression to atmospheric pressure triggers immediate aggregation for the mutants in contrast to a slow aggregation process for the wild-type, as observed by Fourier-transform infrared spectroscopy. The temperature-induced transition leads to aggregation of all rPrPs, but the unfolding temperature is lower for the rPrP amino-terminal deletion mutants. The higher susceptibility to pressure of the amino-terminal deletion mutants can be explained by a change in hydration and cavity distribution. Taken together, our results show that the amino-terminal region has a pivotal role on the development of prion misfolding and aggregation. 相似文献
30.
Rogelio Perez-Padilla Fernando C. Wehrmeister Bartolome R. Celli Maria Victorina Lopez-Varela Maria Montes de Oca Adriana Mui?o Carlos Talamo Jose R. Jardim Gonzalo Valdivia Carmen Lisboa Ana Maria B. Menezes for the PLATINO Team 《PloS one》2013,8(8)