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991.
The importance of the epidermal permeability barrier (EPB) in protecting the mammalian species against harmful UV irradiation, microorganism invasion and water loss is well recognized, as is the role of calcium (Ca(2+)) in keratinocyte differentiation, cell-cell contact and the EPB. In a previous study, we reported that the overexpression of the Ca(2+)-sensing receptor (CaSR) in the undifferentiated basal cells of the epidermis induced a modified epidermal differentiation program including an accelerated EPB formation in transgenic mice, suggesting a role for CaSR signaling in the differentiation of embryonic epidermal cells during development. We now describe the expression profile of claudins (Cldns) and keratin markers in the accelerated EPB formation of K14-CaSR transgenic mice during development as compared to the wild type from E12.5 to newborn stages. Our data show that the transgenic epidermis undergoes an advanced epidermal differentiation program as compared to the wild type as evidenced morphologically as well as by the expression of K14, K1, loricrin, Cldn6, Cldn18 and Cldn11. In addition, we report for the first time the sequential expression of Cldns in epidermal development and describe that the localization of some Cldns change within the epidermis as it matures. Furthermore, we demonstrate that Cldn6 is expressed very early in epidermal morphogenesis, followed by Cldn18, Cldn11 and Cldn1. 相似文献
992.
Shakleya DM Jansson LM Huestis MA 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,856(1-2):267-272
A validated, quantitative LC-APCI-MS/MS method for methadone, EDDP and EMDP in 200-microL plasma is presented. Specimen preparation was limited to protein precipitation and centrifugation. Chromatographic separation was achieved on a Synergi Hydro-RP 80A (50 mm x 2.0 m, 4 microm) column with gradient elution. The assay was linear from 1 to 500 ng/mL, with intra- and inter-assay accuracy >or=87.5% and intra- and inter-assay precision <13.4% R.S.D. and recovery >or=87.5% for all analytes at 40 ng/mL. This analytical method is suitable for the accurate and precise determination of methadone and metabolites in human plasma specimens. 相似文献
993.
Thorpe JD Duan X Forrest R Lowe K Brown L Segal E Nelson B Anderson GL McIntosh M Urban N 《PloS one》2007,2(12):e1281
Background
Evaluating diagnostic and early detection biomarkers requires comparing serum protein concentrations among biosamples ascertained from subjects with and without cancer. Efforts are generally made to standardize blood processing and storage conditions for cases and controls, but blood sample collection conditions cannot be completely controlled. For example, blood samples from cases are often obtained from persons aware of their diagnoses, and collected after fasting or in surgery, whereas blood samples from some controls may be obtained in different conditions, such as a clinic visit. By measuring the effects of differences in collection conditions on three different markers, we investigated the potential of these effects to bias validation studies.Methodology and Principle Findings
We analyzed serum concentrations of three previously studied putative ovarian cancer serum biomarkers–CA 125, Prolactin and MIF–in healthy women, women with ovarian cancer undergoing gynecologic surgery, women undergoing surgery for benign ovary pathology, and women undergoing surgery with pathologically normal ovaries. For women undergoing surgery, a blood sample was collected either in the clinic 1 to 39 days prior to surgery, or on the day of surgery after anesthesia was administered but prior to the surgical procedure, or both. We found that one marker, prolactin, was dramatically affected by collection conditions, while CA 125 and MIF were unaffected. Prolactin levels were not different between case and control groups after accounting for the conditions of sample collection, suggesting that sample ascertainment could explain some or all of the previously reported results about its potential as a biomarker for ovarian cancer.Conclusions
Biomarker validation studies should use standardized collection conditions, use multiple control groups, and/or collect samples from cases prior to influence of diagnosis whenever feasible to detect and correct for potential biases associated with sample collection. 相似文献994.
Objective: To assess the association of dietary fat and weight gain among adult women and to investigate whether offspring of overweight parents have a greater predisposition to weight gain due to intake of dietary fat. Research Methods and Procedures: This was an 8‐year follow‐up of 41,518 women in the Nurses’ Health Study (NHS), a population‐based, prospective cohort. The women were 41 to 68 years of age, free of cardiovascular disease, cancer, and diabetes in 1986 when “baseline” weight and diet were assessed. Eight years later (1994), changes in weight and dietary intake were assessed. Linear regression models were used to relate change in weight to fat intake and change in fat intake, using the percentage of energy from carbohydrate as the comparison, adjusted for age, BMI in 1986, leisure time physical activity, time spent sitting, percent of calories from protein, and change in percentage of calories from protein. Results: Overall, there was a weak positive association between total fat intake (β = 0.11) and weight gain. Increases in monosaturated and polyunsaturated fat were not associated with weight gain, but increases in animal fat, saturated fat, and trans fat had a positive association with weight change. There was not strong evidence of effect modification by parental weight status (p = 0.7 to 0.8 for percentage of calories from total fat, animal fat, and vegetable fat); however, the associations were stronger among the overweight compared with leaner women (p < 0.05 for percentage of calories from each type of fat). Among overweight women, for every one percentage increase in percentage of calories from trans fat, women gained an additional 2.3 lb (95% confidence interval, 1.80 to 2.86). Conclusion: Our results show that, overall, percent of calories from fat has only a weak positive association with weight gain; however, percentage of calories from animal, saturated, and trans fat has stronger associations. There was no clear evidence that the diet‐weight gain association was stronger among offspring of overweight parents, but dietary fat was associated with greater weight gain among overweight women. 相似文献
995.
996.
Insularity and the determinants of lizard population density 总被引:2,自引:0,他引:2
The relative effects of resource availability and partitioning on animal population density are unresolved yet central to ecology and conservation. Species-depauperate islands offer an intriguing test case. Across 643 lizard populations from around the world, local abundances are one order of magnitude higher on islands than on mainlands, even when controlled for resource availability. On mainlands, predator and competitor richness only weakly correlate with lizard densities. On islands, sharp reductions in predator and competitor richness are the dominant drivers of lizard abundance. Our results demonstrate the dramatic effect insularity has on the interplay between biotic and abiotic control of animal abundances and the heightened sensitivity of island communities to species' losses and gains. 相似文献
997.
Lauren N. Kajiura Scott D. Stewart John Dresios Catherine F. T. Uyehara 《Journal of biomolecular techniques》2015,26(4):118-124
Molecular detection of microbial pathogens in clinical samples requires the application of efficient sample lysis protocols and subsequent extraction and isolation of their nucleic acids. Here, we describe a simple and time-efficient method for simultaneous extraction of genomic DNA from gram-positive and -negative bacteria, as well as RNA from viral agents present in a sample. This method compared well with existing bacterial- and viral-specialized extraction protocols, worked reliably on clinical samples, and was not pathogen specific. This method may be used to extract DNA and RNA concurrently from viral and bacterial pathogens present in a sample and effectively detect coinfections in routine clinical diagnostics. 相似文献
998.
Ewa Bielczyk-Maczyńska Laure Lam Hung Lauren Ferreira Tobias Fleischmann Félix Weis Antonio Fernández-Pevida Steven A. Harvey Neha Wali Alan J. Warren Inês Barroso Derek L. Stemple Ana Cvejic 《PLoS genetics》2015,11(12)
Ribosome biogenesis is a ubiquitous and essential process in cells. Defects in ribosome biogenesis and function result in a group of human disorders, collectively known as ribosomopathies. In this study, we describe a zebrafish mutant with a loss-of-function mutation in nol9, a gene that encodes a non-ribosomal protein involved in rRNA processing. nol9
sa1022/sa1022 mutants have a defect in 28S rRNA processing. The nol9
sa1022/sa1022 larvae display hypoplastic pancreas, liver and intestine and have decreased numbers of hematopoietic stem and progenitor cells (HSPCs), as well as definitive erythrocytes and lymphocytes. In addition, ultrastructural analysis revealed signs of pathological processes occurring in endothelial cells of the caudal vein, emphasizing the complexity of the phenotype observed in nol9
sa1022/sa1022 larvae. We further show that both the pancreatic and hematopoietic deficiencies in nol9
sa1022/sa1022 embryos were due to impaired cell proliferation of respective progenitor cells. Interestingly, genetic loss of Tp53 rescued the HSPCs but not the pancreatic defects. In contrast, activation of mRNA translation via the mTOR pathway by L-Leucine treatment did not revert the erythroid or pancreatic defects. Together, we present the nol9
sa1022/sa1022 mutant, a novel zebrafish ribosomopathy model, which recapitulates key human disease characteristics. The use of this genetically tractable model will enhance our understanding of the tissue-specific mechanisms following impaired ribosome biogenesis in the context of an intact vertebrate. 相似文献
999.
Lauren E. Mokry Stephanie Ross Omar S. Ahmad Vincenzo Forgetta George Davey Smith Aaron Leong Celia M. T. Greenwood George Thanassoulis J. Brent Richards 《PLoS medicine》2015,12(8)
BackgroundObservational studies have demonstrated an association between decreased vitamin D level and risk of multiple sclerosis (MS); however, it remains unclear whether this relationship is causal. We undertook a Mendelian randomization (MR) study to evaluate whether genetically lowered vitamin D level influences the risk of MS.ConclusionsA genetically lowered 25OHD level is strongly associated with increased susceptibility to MS. Whether vitamin D sufficiency can delay, or prevent, MS onset merits further investigation in long-term randomized controlled trials. 相似文献
1000.