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931.
Perry JR Voight BF Yengo L Amin N Dupuis J Ganser M Grallert H Navarro P Li M Qi L Steinthorsdottir V Scott RA Almgren P Arking DE Aulchenko Y Balkau B Benediktsson R Bergman RN Boerwinkle E Bonnycastle L Burtt NP Campbell H Charpentier G Collins FS Gieger C Green T Hadjadj S Hattersley AT Herder C Hofman A Johnson AD Kottgen A Kraft P Labrune Y Langenberg C Manning AK Mohlke KL Morris AP Oostra B Pankow J Petersen AK Pramstaller PP Prokopenko I Rathmann W Rayner W Roden M Rudan I Rybin D 《PLoS genetics》2012,8(5):e1002741
Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m2) compared to obese cases (BMI≥30 Kg/m2). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m2) or 4,123 obese cases (BMI≥30 kg/m2), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and combined effects of SNPs representing 36 type 2 diabetes loci. After combining data from discovery and replication datasets, we identified two signals not previously reported in Europeans. A variant (rs8090011) in the LAMA1 gene was associated with type 2 diabetes in lean cases (P = 8.4×10−9, OR = 1.13 [95% CI 1.09–1.18]), and this association was stronger than that in obese cases (P = 0.04, OR = 1.03 [95% CI 1.00–1.06]). A variant in HMG20A—previously identified in South Asians but not Europeans—was associated with type 2 diabetes in obese cases (P = 1.3×10−8, OR = 1.11 [95% CI 1.07–1.15]), although this association was not significantly stronger than that in lean cases (P = 0.02, OR = 1.09 [95% CI 1.02–1.17]). For 36 known type 2 diabetes loci, 29 had a larger odds ratio in the lean compared to obese (binomial P = 0.0002). In the lean analysis, we observed a weighted per-risk allele OR = 1.13 [95% CI 1.10–1.17], P = 3.2×10−14. This was larger than the same model fitted in the obese analysis where the OR = 1.06 [95% CI 1.05–1.08], P = 2.2×10−16. This study provides evidence that stratification of type 2 diabetes cases by BMI may help identify additional risk variants and that lean cases may have a stronger genetic predisposition to type 2 diabetes. 相似文献
932.
Gail V. Matthews Rachel J. Ali Anchalee Avihingsanon Janaki Amin Rachel Hammond Scott Bowden Sharon R. Lewin Joe Sasadeusz Margaret Littlejohn Stephen L. Locarnini Kiat Ruxrungtham Gregory J. Dore 《PloS one》2013,8(4)
Objective
Anti-HBe seroconversion and HBsAg loss are important therapeutic endpoints in patients with hepatitis B virus (HBV) infection. Quantitative measures of hepatitis B surface antigen (qHBsAg) and e antigen (qHBeAg) have been identified as potentially useful indicators of therapeutic response in HBV monoinfection. The aim of this study was to examine serological change including quantitative biomarkers in HIV-HBV coinfected patients initiating HBV active antiretroviral therapy (ART).Methods
HIV-HBV coinfected individuals from Thailand were followed for up to 168 weeks post ART. Rates and associations of qualitative serological change were determined. Longitudinal changes in qHBsAg and qHBeAg were measured and their utility as predictors of response examined.Results
Forty seven patients were included of whom 27 (57%) were HBeAg positive at baseline. Median CD4 count was 48 cells/mm3. Over a median follow-up of 108 weeks 48% (13/27) lost HBeAg, 12/27 (44%) achieved anti-HBe seroconversion and 13% (6/47) HBsAg loss. Anti-HBe seroconversion was associated with higher baseline ALT (p = 0.034), lower qHBsAg (p = 0.015), lower qHBeAg (p = 0.031) and greater HBV DNA decline to week 24 (p = 0.045). Sensitivity and specificity for qHBsAg and qHBeAg decline of >0.5 log at week 12 and >1.0 log at week 24 were high for both anti-HBe seroconversion and HBsAg loss.Conclusions
Rates of serological change in these HIV-HBV coinfected individuals with advanced immunodeficiency initiating HBV-active ART were high. Baseline and on treatment factors were identified that were associated with a greater likelihood of subsequent anti-HBe seroconversion, including both quantitative HBsAg and HBeAg, suggesting these biomarkers may have utility in this clinical setting. 相似文献933.
934.
Gurdyal S. Besra David E. Minnikin Amin Sharif John L. Stanford 《FEMS microbiology letters》1990,66(1-3):11-13
Abstract Dtacyl phtluodlolone A and phenolphthtodlo-lone A hpids were isolated from two stratus of Mycobactertum ulcerans . The dlol umts of the phthione A and phenolphth]odlolone A components were shown to have erythro stercochemistry by infrared spectroscopy and proton nuclear magnetic resonance of an acetal derivative This stereoehemistry is shared only by related dvols from M. marmum , the dhols from M. boys, M kansasu, M leprae and M. luberculosiss having threo stereochemlstry. 相似文献
935.
936.
Alijani S Balaghi S Mohammadifar MA 《International journal of biological macromolecules》2011,49(4):471-479
In this study, Iranian gum tragacanth (GT) exudates from Astragalus fluccosus (AFG) and Astragalus gossypinus (AGG) were irradiated at 3, 7, 10 and 15 kGy. Fourier transform infrared spectroscopy (FTIR) data showed that irradiation did not induce changes in the chemical structure of either type of gum. Although particle size distribution and both steady shear and dynamic rheological properties were considerably affected by the irradiation process, the magnitude of the effect of irradiation on each of the rheological and size variables was different for the hydrocolloids. For instance, for AGG, increasing the irradiation dose from 3 to 10 kGy, the d(0.5) and D[3,2] values were reduced by one-sixth to one-eighth fold. Colour measurement revealed that the radiation process led to an increase in the yellow index and b* values for both types of GT in powder form, but it was more pronounced for AGG samples. Irradiation led to an approximate 13-fold increase in redness in AFG. Surface and shape changes of the gum crystals were studied by scanning electron microscope (SEM) and a smoother surface for irradiated samples was detected. The notable changes in functional properties of each variety of irradiated gum should be taken into consideration before using the radiation technology as a commercial tool for sterilisation. 相似文献
937.
It is now widely accepted that dietary phytochemicals inhibit cancer progression and enhance the effects of conventional chemotherapy.
In this report, we comparatively studied the cellular and molecular aspects of apoptosis induction by the methanolic extract
of Baneh fruit skin in comparison to Doxorubicin (Dox), a well-known anticancer drug, in human breast cancer T47D cells. The MTT assay was used to determine the antiproliferative effects. The flow cytometric and microscopic analyses were done
to evaluate the apoptosis induction. Furthermore, western blot analyses have been done to study the role of key molecular
players of apoptosis including caspase 3 and PARP. The Baneh extract showed strong antiproliferative activity against T47D cells in a dose- and time-dependent manner that was comparable
to and even stronger than Dox in certain concentrations. Analysis of Baneh-treated cells by flow cytometry and fluorescence microscopy indicated strong apoptosis induction and nuclear morphological
alterations similar to or greater than Dox. Finally, molecular analysis of apoptosis by western blotting proved activation
of caspase 3 followed by poly ADP ribose polymerase (PARP) cleavage more efficiently in Baneh than in Dox treated cancer cells. These findings indicate that Baneh extract contains phytochemicals which act as inhibitor of cell proliferation and inducer of apoptosis in human breast cancer
T47D cells that makes it a potentially good candidate for new anticancer drug development. 相似文献
938.
Amin KM Awadalla FM Eissa AA Abou-Seri SM Hassan GS 《Bioorganic & medicinal chemistry》2011,19(20):6087-6097
The main objective of the present work depends on the hybridization of coumarin moiety as a vasorelaxant scaffold and pyrimidine ring with known potential cardiovascular activity in order to prepare some new potent antihypertensive candidates. Hence, two groups of pyrimidinyl coumarin derivatives were synthesized and evaluated for their vasorelaxing activity. These compounds were prepared via two routes; either preparation of the guanidinocoumarin 4 followed by a cocktail of cyclization reactions to yield a different array of 6-(substituted pyrimidin-2-yl)aminocoumarins 5-17, or through cyclization of the precursor chalcones 22a-g with guanidine hydrochloride to generate the corresponding final compounds, 8-(6-aryl-2-aminopyrimidin-4-yl)-7-methoxycoumarins 23a-g. The effect of these compounds and the coumarin intermediates 3, 4, 21 and 22a-g on nor-epinephrine induced contracture in thoracic rat aortic rings was investigated using prazocin as reference drug. Several derivatives showed promising activities either equal or even better than that of prazocin (IC(50) 0.487 mM). The most prospective compounds; the pyrimidinylamino coumarin derivatives 8, 17 (IC(50) 0.411, IC(50) 0.421 mM) and the chalcones 22b, 22e (IC(50) 0.371, 0.374 mM) that displayed the highest activity can be a base for lead optimization and simple but efficient design of new compounds. 2D-QSAR analysis was applied to find a correlation between the experimental vasorelaxant activities of the newly synthesized coumarin derivatives and their different physicochemical parameters. The result of this study showed that the increase in aqueous solubility while retaining good hydrophobic character of the overall molecule is the key for maintaining high relaxation activity. 相似文献
939.
Spencer J Amin J Callear SK Tizzard GJ Coles SJ Coxhead P Guille M 《Metallomics : integrated biometal science》2011,3(6):600-608
(E)- and (Z)-3-Ferrocenylmethylidene-1,3-dihydro-2H-indol-2-ones 1 have been structurally modified in order to explore SAR against a range of kinases. Of note is the submicromolar to low micromolar inhibition of DYRK3 and 4 by a number of complexes. Screening using Xenopus embryos showed some of the compounds to have potent antiangiogenisis activity. 相似文献
940.
Adipocyte enhancer binding protein 1 (AEBP1) is a multifunctional protein that negatively regulates the tumor suppressor PTEN and IκBα, the inhibitor of NF-κB, through protein-protein interaction, thereby promoting cell survival and inflammation. Mice homozygous for a disrupted AEBP1 gene developed to term but showed defects in growth after birth. AEBP1(-/-) females display lactation defect, which results in the death of 100% of the litters nursed by AEBP1(-/-) dams. Mammary gland development during pregnancy appears normal in AEBP1(-/-) dams; however these mice exhibit expansion of the luminal space and the appearance of large cytoplasmic lipid droplets (CLDs) in the mammary epithelial cells at late pregnancy and parturition, which is a clear sign of failed secretory activation, and accumulation of milk proteins in the mammary gland, presumably reflecting milk stasis following failed secretory activation. Eventually, AEBP1(-/-) mammary gland rapidly undergoes involution at postpartum. Stromal restoration of AEBP1 expression by transplanting wild-type bone marrow (BM) cells is sufficient to rescue the mammary gland defect. Our studies suggest that AEBP1 is critical in the maintenance of normal tissue architecture and function of the mammary gland tissue and controls stromal-epithelial crosstalk in mammary gland development. 相似文献