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991.
Alberton EH Damazio RG Cazarolli LH Chiaradia LD Leal PC Nunes RJ Yunes RA Silva FR 《Chemico-biological interactions》2008,171(3):355-362
A series of chalcone derivatives from 3,4-methylenedioxybenzaldehyde and substituted acetophenones have been synthesized and investigated as antihyperglycemic agents in a glucose loaded animal model. Chalcones with biological activity were compared with lispro, regular insulin and tolbutamide effects on serum glucose levels. Compound 01, without substituent in the A-ring was not able to change glycemic levels. On the other hand, compounds 03, 04, 05, 09 and 10 with substitutions at position 3' and/or 4' in the A-ring caused significant reduction in serum glucose levels. Concerning the antihyperglycemic effect, compounds 03 and 05 (methoxy substituent) inhibited the hyperglycemia induced by glucose around 96% similar to that demonstrated for lispro insulin and tolbutamide at 60 min. A rapid and lasting antihyperglycemic effect was found with compound 09 and 10 (nitro substituent). In conclusion, besides the nature of the functional groups electron-donor substituent, as methoxy and hydroxyl or electron-acceptor, as nitro groups, the position of the group may be mandatory for biological activity. 相似文献
992.
The structure of unique colorless needle crystals growing from the surface mycelium of the basidiomycete Quambalaria cyanescens and identified as (+)-globulol was followed by mass spectrometry, X-ray diffraction, and polarimetry. The mechanism of (+)-globulol fragmentation is proposed based on collision induced dissociation mass spectrometry. X-Ray analysis revealed that crystal packing is governed by hydrogen bond O-H.....O connecting the molecules into an infinite helix along a 3-fold screw axis propagating along the longest dimension of the needle crystal (c-axis of the unit cell). The X-ray diffraction data correspond well with the proposed structure determined by mass spectrometry. 相似文献
993.
Laffly E Pelat T Cédrone F Blésa S Bedouelle H Thullier P 《Journal of molecular biology》2008,378(5):1094-1103
The enhancement of antibody affinity by mutagenesis targeting only complementarity determining regions has the advantage of respecting the framework regions, which are important for tolerance if clinical use is envisaged. Here, starting from a Fab (antigen-binding fragment; 35PA83) capable of neutralizing the lethal toxin of anthrax and having an affinity of 3.4 nM for its antigen, a phage-displayed library of variants where all six complementarity determining regions (73 positions) were targeted for mutagenesis was built. This library contained 5 × 108 variants, and each variant carried four mutations on average. The library was first panned with adsorbed antigen and washes of increasing stringency. It was then screened in parallel with either small concentrations of soluble biotinylated antigen or adsorbed antigen and long elution times in the presence of soluble antigen. The stringencies of both selections were pushed as far as possible. Compared with 35PA83, the best selected clone had an affinity enhanced 19-fold, to 180 pM, and its 50% inhibitory concentration was decreased by 40%. The results of the two selection methods were compared, and the generality of these methods was considered. 相似文献
994.
Bahram Hosseini-Maaf ?sa Hellberg Maria J Rodrigues M Alan Chester Martin L Olsson 《BMC genetics》2003,4(1):17
Background
Since the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood-group ABO locus, polymorphisms due to ethnic and/or phenotypic variations have been reported. Some subgroups have been explained at the molecular level, but unresolved samples are frequently encountered in the reference laboratory. 相似文献995.
Johanna Deinum Lars Gustavsson Erika Gyzander Mari Kullman-Magnusson sa Edstrm Robert Karlsson 《Analytical biochemistry》2002,300(2):152-162
The binding of a series of low-molecular-mass, active-site-directed thrombin inhibitors (399-575 Da) to human alpha-thrombin was investigated by surface plasmon resonance technology (BIACORE), stopped-flow spectrophotometry, and isothermal titration microcalorimetry (ITC). The equilibrium constants K(D) (nM to microM range) at 25 degrees C obtained from the BIACORE analysis correlated well with the inhibition constants K(i) in a chromogenic inhibition assay. The interactions between thrombin and three potent inhibitors, melagatran, inogatran, and CH-248, were further investigated at temperatures between 278 and 310K. A one-to-one binding stoichiometry found with ITC was supported by BIACORE data. K(i) and K(D) values increased with the temperature, mainly due to higher values for dissociation rate constants. The changes in enthalpy, DeltaH, and entropy, DeltaS, determined from the linear van't Hoff plots (R coefficient > 0.99), were linearly correlated by chemical compensation. Both techniques indicated clear differences in DeltaS for the three inhibitors, with a strong correlation to the number of rotational bonds. Immobilization of thrombin increased the binding stability at higher temperature and reduced the DeltaH by 20 kJ mol(-1). DeltaH values obtained from the inhibition kinetics and BIACORE were thus not identical, but correlated well with ITC data obtained at 37 degrees C. The two thermodynamic techniques allowed further differentiation between compounds of similar affinity; furthermore, kinetic analysis, hence analysis of the transition state, is complementary to ITC. A direct BIACORE binding assay might be a useful alternative to more elaborate inhibition studies. 相似文献
996.
Åsa Olsson Jens Peter Garne Ingrid Tengrup Sophia Zackrisson Jonas Manjer 《Cancer epidemiology》2009,33(1):9-15
Objectives: Overweight is associated with advanced stage at diagnosis in breast cancer patients. This could be explained by specific tumour characteristics or tumour promoting factors in the obese, but a diagnostic delay could also be of importance. Mammographic screening has caused a change towards diagnosis of less advanced tumours. This study investigates invitation to mammographic screening and the association between overweight and tumour size/axillary lymph node involvement at breast cancer diagnosis in postmenopausal women. Methods: In 1976 a randomized mammographic screening trial, inviting 50% of all women aged 45–69 was set up in Malmö, Sweden. The present analysis examined overweight (body mass index ≥25) as a determinant for large tumours (>20 mm) and axillary lymph node involvement in postmenopausal women. These associations were studied separately in patients diagnosed prior to the mammographic screening trial, in invited women and in non-invited subjects (controls). In all, 2478 postmenopausal women were diagnosed with invasive breast cancer in these groups between 1961 and 1991. Logistic regression analysis allowed adjustment for other potential determinants of tumours size and axillary lymph node involvement. Results: In women diagnosed before the onset of the screening trial and in women not invited to mammography in the trial (controls), overweight was positively associated with large tumour size and axillary node involvement. There was no statistically significant association between overweight and these factors in women invited to mammographic screening. Conclusion: Invitation to mammographic screening may be particularly important for overweight postmenopausal women in order to detect breast tumours early. 相似文献
997.
Impact of herbivory and pollination on performance and competitive ability of oilseed rape transformed for pollen beetle resistance 总被引:1,自引:0,他引:1
Competitive ability of transgenic oilseed rape transformed with a pea lectin gene was estimated by comparisons of its performance
when grown in a mixture with its non-transgenic counterpart and when grown singly, with and without pollen beetles present.
The experiments were carried out in cages, once with bumblebees as pollinators and once without. In the absence of herbivory
but with the presence of bumblebees, singly grown plant lines without lectin generally performed better than lines with lectin.
Pollen beetles affected plant growth and reproduction, but there were no consistent differences between the lectin and non-lectin
plant lines indicating that the transgenic trait did not protect plants from pest attack. Herbivory reduced the number of
seeds when bumblebees were present. In the absence of bumblebees, however, plants produced more seeds with pollen beetles
than without, indicating that some pollination was carried out by the beetles. Efficient pollination affected the competitive
abilities of the lines; lectin lines were more competitive with bumblebees present and the reverse was true when bumblebees
were absent. In the presence of bumblebees, lectin lines gained from being grown mixed with its non-transgenic counterpart.
Because the transgenic plants expressed pea lectin in developing pollen it is possible that pollen quality in those plants
was reduced, which may explain why the lectin lines had an advantage over non-lectin lines when exchange of pollen between
the two plant types was facilitated by bumblebees. 相似文献
998.
The technique of using luminescent oligo-thiophenes and luminescent conjugated poly-thiophenes to monitor biological processes
has gained increased interest from scientists within different research areas, ranging from organic chemistry and photo-physics
to biology since its introduction. The technique is generally straightforward and requires only standard equipment, and the
result is available within minutes from sample preparation. In this review, the syntheses of oligo and polythiophenes developed
over the last decades are discussed. Furthermore, the utilization of these molecular agents for exploring biological events,
e.g., DNA hybridization or protein misfolding events, are covered. 相似文献
999.
Isabel Rodrigues Carolina Ferreira Joana Gonalves Luísa Carvalho Jorge Oliveira Carla Castro ngelo Oliveira 《Reports of Practical Oncology and Radiotherapy》2021,26(4):535
BackgroundSalvage radiotherapy (sRT) is the main potentially curative treatment after biochemical failure/locoregional relapse post-radical prostatectomy (RP). The aim of the study was to characterize the population who underwent sRT after RP at our Department, to understand the influence of several potential prognosis factors, and to determine possible optimization strategies.Materials and methodsWe retrospectively analyzed patients undergoing sRT at our department between 2012 and 2017, evaluating patient, tumor and treatment characteristics, restaging procedures and clinical outcomes — namely biochemical relapse-free survival (BC-RFS), clinical relapse-free survival (C-RFS), additional hormone therapy-free survival (HT-FS) and overall survival (OS). We assessed potential prognostic factors by univariate and multivariate models (MVA).ResultsWe included 277 patients (median age 68 years). Median pre-sRT PSA was > 0.5ng/mL in 54.9%. All underwent prostate bed irradiation. Pelvic lymph nodes were included in 9.7%. Outcome analysis was performed for 264 patients (35.6 months median follow-up). At 3 years, BC-RFS was 61.4%, C-RFS was 81.3%, HT-FS was 79.9% and OS was 96.6%. Most relapses occurred in regional lymph nodes only (47.9% patients who relapsed). On MVA, lymphovascular invasion, advanced pT-stages and negative margins negatively influenced BC-RFS (p = 0.029, p = 0.002 and p < 0.001) and HT-FS (p = 0.001, p = 0.029 and p = 0.002). C-RFS was worsened by lymphovascular invasion (p = 0.009) and negative margins (p = 0.015). These had no effect on OS. BC-RFS and HT-FS were improved when sRT started while PSA ≤ 0.5 ng/mL (p < 0.05).ConclusionLymphovascular invasion, higher pT-stages and negative margins negatively affected prognosis. An early start of sRT (PSA ≤ 0.5 ng/mL) predicted better BC-RFS and HT-FS. 相似文献
1000.
Internal diversification of non‐Sub‐Saharan haplogroups in Sahelian populations and the spread of pastoralism beyond the Sahara
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