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81.
The biogenetic origin of the isoprenoid building blocks of the sesquiterpene germacrene D was studied in Solidago canadensis. Feeding experiments were carried out with 1-[5,5-D(2)]deoxy-D-xylulose-5-phosphate (D(2)-DOXP), [5-13C]mevalonolactone (13C-MVL) and [1-13C]-D-glucose. The hydrodistillate of a cut shoot fed with D(2)-DOXP was investigated by enantio-MDGC-MS and the volatile fraction of a shoot supplied with 13C-MVL was examined by GC-C-IRMS. The incorporation of [1-13C]-D-glucose was analyzed by quantitative 13C NMR spectroscopy after isolation of germacrene D from the essential oil. Our labeling studies revealed that the biosynthesis of the C-15 skeleton of sesquiterpene germacrene D in Solidago canadensis proceeds predominantly via the methylerythritol phosphate pathway.  相似文献   
82.
Covalently closed circular RNA molecules (circRNAs) have recently emerged as a class of RNA isoforms with widespread and tissue specific expression across animals, oftentimes independent of the corresponding linear mRNAs. circRNAs are remarkably stable and sometimes highly expressed molecules. Here, we sequenced RNA in human peripheral whole blood to determine the potential of circRNAs as biomarkers in an easily accessible body fluid. We report the reproducible detection of thousands of circRNAs. Importantly, we observed that hundreds of circRNAs are much higher expressed than corresponding linear mRNAs. Thus, circRNA expression in human blood reveals and quantifies the activity of hundreds of coding genes not accessible by classical mRNA specific assays. Our findings suggest that circRNAs could be used as biomarker molecules in standard clinical blood samples.  相似文献   
83.
Lacerta pamphylica and Lacerta trilineata are two currently recognized green lizard species with a historically problematic taxonomy. In cases of tangled phylogenies, next-generation sequencing and double-digest restriction-site-associated DNA protocols can provide a wealth of genomic data and resolve difficult taxonomic issues. Here, we generated genome-wide SNPs and mitochondrial sequences, and applied molecular species delimitation approaches to provide a stable taxonomy for the Aegean green lizards. Mitochondrial gene trees, genetic cluster delimitation and population structure analyses converged into recognizing the populations of (a) L. pamphylica, (b) east Aegean islands, Anatolia and Thrace (diplochondrodes lineage), (c) central Aegean islands (citrovittata), and (d) remaining Balkan populations and islands (trilineata), as separate clusters. Phylogenomic analyses revealed a split into two major clades, east and west of the Aegean Barrier, unambiguously showing a sister–clade relationship between pamphylica and diplochondrodes, rendering L. trilineata paraphyletic. Species delimitation models were tested in a Bayesian framework using the genomic SNPs: lumping all populations into a single ‘species’ had the lowest likelihood but the current taxonomy was also outperformed by all other models. All lines of evidence support the Pamphylian green lizard as a valid species; thus, east Aegean L. trilineata should also be considered a distinct species under the name Lacerta diplochondrodes. Finally, evidence from the mitochondrial and nuclear genomes is overwhelmingly in favour of recognizing the morphologically distinct Cycladian green lizards as a distinct species. We propose their elevation to full species under the name Lacerta citrovittata. All remaining insular and continental populations of the Balkan Peninsula represent the species L. trilineata.  相似文献   
84.
85.
Chronic kidney disease (CKD) is the end-point of a number of renal and systemic diseases. The high incidence and financial burden of CKD makes it imperative to diagnose CKD at early stages when therapeutic interventions are far more effective. A key component of CKD is the development of renal fibrosis. Renal fibrosis is a complex process, associated with many cell types and pathways, resulting in structural and functional alterations. Identification of specific biomarkers of renal fibrosis may thus not only help us to understand the pathophysiological mechanisms involved in this process, but also improve diagnosis in the clinic. In this review, the existing literature on proteomic approaches to study renal fibrosis is presented and evaluated. The importance of using animal models along with patient material is discussed and future directions, considered key to this field, are proposed.  相似文献   
86.
ADP-ribosyltransferases (ADP-RTs) use NAD(+) to transfer an ADP-ribosyl group to target proteins. Although some ADP-RTs are bacterial toxins only few inhibitors are known. Here we present the development of fluorescence-based assays and a focussed library screening using kinase inhibitors as a new approach towards inhibitors of ADP-RTs. Different screening setups were established using surrogate small molecule substrates or the quantitation of the cofactor NAD(+). Proof-of-principle screening experiments were performed using a kinase inhibitor library in order to target the NAD(+) binding pockets. This led to the discovery of structurally different lead inhibitors for the mono-ADP-ribosyltransferases Mosquitocidal toxin (MTX) from Bacillus sphaericus SSII-1, C3bot toxin from Clostridium botulinum and CDTa from Clostridium difficile. The interaction of the inhibitors with the toxin proteins was analyzed by means of docking and binding free energy calculations. Binding at the nicotinamide subpocket, which shows a significant difference in the three enzymes, is used to explain the selectivity of the identified inhibitors and offers an opportunity for further development of potent and selective inhibitors.  相似文献   
87.
The aim of our study was to evaluate the effect of BMI on the change in circulating sex hormone in postmenopausal women during 6 months of oral continuous combined low-dose hormone therapy (HT). Fifty postmenopausal women were allocated to receive daily one tablet containing combination of 17β-estradiol (1 mg)/norethindrone acetate (0.5 mg) for 6 months. Serum levels of follicle-stimulating hormone (FSH), estradiol, total testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), free estrogen index (FEI), Δ4-androstendione (Δ4A), and dehydroepiandrosterone sulfate were assessed at baseline and at the end of 6 months. Mean absolute values and percent changes from baseline were compared between lean and overweight women. Mean FSH decreased and mean 17β-estradiol increased significantly in both groups (FSH lean: 82.3 ± 26.7 decreased to 45.0 ± 17.0 mIU/ml, P = 0.0001; FSH overweight: 85.5 ± 22.1 decreased to 52.3 ± 23.8 mIU/ml, P = 0.003; P between groups = 0.661; E2 lean: 23.24 ± 12.55 increased to 53.62 ± 28.29 pg/ml, P = 0.006; E2 overweight: 24.17 ± 10.88 increased to 68.36 ± 53.99 pg/ml, P = 0.0001; P between groups = 0.619). Lean individuals had statistically significant higher increments of FAI and specifically FEI compared to overweight (FEI lean; 0.14 ± 0.09 increased to 0.29 ± 0.14, P = 0.009; overweight 0.23 ± 0.18 increased to 0.52 ± 0.40, P = 0.126; P between groups = 0.034). Although BMI does not affect total 17β-estradiol changes, free sex steroid concentrations increase more steeply in lean compared to overweight women receiving oral low-dose HT.  相似文献   
88.
The objective of the present experiment was to determine the implications of prenatal undernutrition on the behaviour of juvenile lambs. Dams of one group (C) were fed 100% of the recommended requirements throughout pregnancy, while those of two other groups were fed 50% of the control nutrient allowance during the first 30 days of pregnancy (R1) or 50% of the control nutrient allowance from days 31–100 of pregnancy (R2). Between 2 and 5 months old, behaviour of lambs was tested by the implementation of 2 types of test: isolation and novelty. There were no statistical differences between lamb treatments in escape behaviour and heart rates during isolation test, or the latency to approach a novel or a familiar object in the novelty test in tests conducted at 2, 3, 4 and 5 months of age.Male lambs showed a tendency of turning to the right-hand side of the test pen, irrespective of treatment group, between the age of 2 and 5 months old. A greater proportion of C compared to R1 males turned right at the age of 2 and 5 months old (P < 0.05). Significant differences concerning laterality were found also between C and R1 female lambs at the age of 2 and 4 months old (P < 0.001), between C and R2 male lambs at the age of 2 months old (P < 0.05), between C and R2 female lambs at the age of 4 and 5 months old (P < 0.01), between R1 and R2 male lambs at the age of 2 and 5 months old (P < 0.05) and between R1 and R2 female lambs at the age of 2 months old (P < 0.001).It is concluded that prenatal undernutrition during different periods of pregnancy had no effect on fear-related behaviour, but effect on laterality at the early stages of lamb age between 2 and 5 months old.  相似文献   
89.

Background

Genes encoding cytokine mediators are prime candidates for genetic analysis in conditions with T-helper (Th) cell disease driven imbalance. Idiopathic Pulmonary Fibrosis (IPF) is a predominantly Th2 mediated disease associated with a paucity of interferon-gamma (IFN-γ). The paucity of IFN-γ may favor the development of progressive fibrosis in IPF. Interleukin-12 (IL-12) plays a key role in inducing IFN-γ production. The aim of the current study was to assess whether the 1188 (A/C) 3'UTR single nucleotide polymorphism (SNP) in the IL-12 p40 subunit gene which was recently found to be functional and the 5644 (G/A) 3' UTR SNP of the IFN-γ gene were associated with susceptibility to IPF.

Methods

We investigated the allelic distribution in these loci in UK white Caucasoid subjects comprising 73 patients with IPF and 157 healthy controls. The SNPs were determined using the polymerase chain reaction in association with sequence-specific primers incorporating mismatches at the 3'-end.

Results

Our results showed that these polymorphisms were distributed similarly in the IPF and control groups

Conclusion

We conclude that these two potentially important candidate gene single nucleotide polymorphisms are not associated with susceptibility to IPF.  相似文献   
90.
The two anomers of O-methyl gluco-2,3-digalloyl esters were synthesized and their antimycotic activity toward yeasts of biomedical importance was evaluated. When used at subinhibitory concentration and regardless of stereochemistry at the anomeric carbon, these compounds enhance the antimycotic activity of Amphotericin B.  相似文献   
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