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991.
A. Sally Davis Daniel S. Chertow Jenna E. Moyer Jon Suzich Aline Sandouk David W. Dorward Carolea Logun James H. Shelhamer Jeffery K. Taubenberger 《The journal of histochemistry and cytochemistry》2015,63(5):312-328
Primary normal human bronchial/tracheal epithelial (NHBE) cells, derived from the distal-most aspect of the trachea at the bifurcation, have been used for a number of studies in respiratory disease research. Differences between the source tissue and the differentiated primary cells may impact infection studies based on this model. Therefore, we examined how well-differentiated NHBE cells compared with their source tissue, the human distal trachea, as well as the ramifications of these differences on influenza A viral pathogenesis research using this model. We employed a histological analysis including morphological measurements, electron microscopy, multi-label immunofluorescence confocal microscopy, lectin histochemistry, and microarray expression analysis to compare differentiated NHBEs to human distal tracheal epithelium. Pseudostratified epithelial height, cell type variety and distribution varied significantly. Electron microscopy confirmed differences in cellular attachment and paracellular junctions. Influenza receptor lectin histochemistry revealed that α2,3 sialic acids were rarely present on the apical aspect of the differentiated NHBE cells, but were present in low numbers in the distal trachea. We bound fluorochrome bioconjugated virus to respiratory tissue and NHBE cells and infected NHBE cells with human influenza A viruses. Both indicated that the pattern of infection progression in these cells correlated with autopsy studies of fatal cases from the 2009 pandemic. 相似文献
992.
An increasingly asked question is ''can we confidently link bats with emerging
viruses?''. No, or not yet, is the qualified answer based on the evidence available.
Although more than 200 viruses - some of them deadly zoonotic viruses - have been
isolated from or otherwise detected in bats, the supposed connections between bats,
bat viruses and human diseases have been raised more on speculation than on evidence
supporting their direct or indirect roles in the epidemiology of diseases (except for
rabies). However, we are convinced that the evidence points in that direction and
that at some point it will be proved that bats are competent hosts for at least a few
zoonotic viruses. In this review, we cover aspects of bat biology, ecology and
evolution that might be relevant in medical investigations and we provide a
historical synthesis of some disease outbreaks causally linked to bats. We provide
evolutionary-based hypotheses to tentatively explain the viral transmission route
through mammalian intermediate hosts and to explain the geographic concentration of
most outbreaks, but both are no more than speculations that still require formal
assessment. 相似文献
993.
Nucleic acid oxidation: an early feature of Alzheimer's disease 总被引:1,自引:0,他引:1
Melissa A. Bradley‐Whitman Michael D. Timmons Tina L. Beckett Michael P. Murphy Bert C. Lynn Mark A. Lovell 《Journal of neurochemistry》2014,128(2):294-304
Studies of oxidative damage during the progression of Alzheimer's disease (AD) suggest its central role in disease pathogenesis. To investigate levels of nucleic acid oxidation in both early and late stages of AD, levels of multiple base adducts were quantified in nuclear and mitochondrial DNA from the superior and middle temporal gyri (SMTG), inferior parietal lobule (IPL), and cerebellum (CER) of age‐matched normal control subjects, subjects with mild cognitive impairment, preclinical AD, late‐stage AD, and non‐AD neurological disorders (diseased control; DC) using gas chromatography/mass spectrometry. Median levels of multiple DNA adducts in nuclear and mitochondrial DNA were significantly (p ≤ 0.05) elevated in the SMTG, IPL, and CER in multiple stages of AD and in DC subjects. Elevated levels of fapyguanine and fapyadenine in mitochondrial DNA suggest a hypoxic environment early in the progression of AD and in DC subjects. Overall, these data suggest that oxidative damage is an early event not only in the pathogenesis of AD but is also present in neurodegenerative diseases in general.
994.
Paulo Gaspar Wouter W. Kallemeijn Anneke Strijland Saskia Scheij Marco Van Eijk Jan Aten Herman S. Overkleeft Andrea Balreira Friederike Zunke Michael Schwake Clara Sá Miranda Johannes M. F. G. Aerts 《Journal of lipid research》2014,55(1):138-145
Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency of LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells of patients with Gaucher disease (GD), a lysosomal storage disorder caused by mutations in the GBA gene. While GD is characterized by the presence of glucosylceramide-laden macrophages, AMRF patients do not show these. We studied the fate of GBA in relation to LIMP2 deficiency by employing recently designed activity-based probes labeling active GBA molecules. We demonstrate that GBA is almost absent in lysosomes of AMRF fibroblasts. However, white blood cells contain considerable amounts of residual enzyme. Consequently, AMRF patients do not acquire lipid-laden macrophages and do not show increased plasma levels of macrophage markers, such as chitotriosidase, in contrast to GD patients. We next investigated the consequences of LIMP2 deficiency with respect to plasma glycosphingolipid levels. Plasma glucosylceramide concentration was normal in the AMRF patients investigated as well as in LIMP2-deficient mice. However, a marked increase in the sphingoid base, glucosylsphingosine, was observed in AMRF patients and LIMP2-deficient mice. Our results suggest that combined measurements of chitotriosidase and glucosylsphingosine can be used for convenient differential laboratory diagnosis of GD and AMRF. 相似文献
995.
Cécile Voisset Néstor García-Rodríguez April Birkmire Marc Blondel Ralf Erik Wellinger 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2014
Cross-complementation studies offer the possibility to overcome limitations imposed by the inherent complexity of multicellular organisms in the study of human diseases, by taking advantage of simpler model organisms like the budding yeast Saccharomyces cerevisiae. This review deals with, (1) the use of S. cerevisiae as a model organism to study human diseases, (2) yeast-based screening systems for the detection of disease modifiers, (3) Hailey–Hailey as an example of a calcium-related disease, and (4) the presentation of a yeast-based model to search for chemical modifiers of Hailey–Hailey disease. The preliminary experimental data presented and discussed here show that it is possible to use yeast as a model system for Hailey–Hailey disease and suggest that in all likelihood, yeast has the potential to reveal candidate drugs for the treatment of this disorder. This article is part of a Special Issue entitled: Calcium signaling in health and disease. Guest Editors: Geert Bultynck, Jacques Haiech, Claus W. Heizmann, Joachim Krebs, and Marc Moreau. 相似文献
996.
Sara Lebiush‐Mordechai Orly Erlich Marcel Maymon Stanley Freeman Tslila Ben‐David Tal Ofek Eric Palevsky Leah Tsror 《Journal of Phytopathology》2014,162(7-8):466-471
In the past 10 years, there has been a substantial increase in reports, from growers and extension personnel, on bulb and root rots in lily (Lilium longiflorum) in Israel. Rot in these plants, when grown as cut flowers, caused serious economic damage expressed in reduction in yield and quality. In lily, the fungal pathogens involved in the rot were characterized as binucleate Rhizoctonia AG‐A, Rhizoctonia solani, Pythium oligandrum, Fusarium proliferatum (white and purple isolates) and F. oxysporum, using morphological and molecular criteria. These fungi were the prevalent pathogens in diseased plants collected from commercial greenhouses. Pathogenicity trials were conducted on lily bulbs and onion seedlings under controlled conditions in a greenhouse to complete Koch's postulates. Disease symptoms on lily were most severe in treatments inoculated with binucleate Rhizoctonia AG‐A, P. oligandrum and F. proliferatum. Plant height was lower in the above treatments compared with the control plants. The least aggressive fungus was R. solani. In artificial inoculations of onion, seedling survival was significantly affected by all fungi. The most pathogenic fungus was F. proliferatum w and the least were isolates of F. oxysporum (II and III). All fungi were successfully re‐isolated from the inoculated plants. 相似文献
997.
Western Flower Thrips (Frankliniella occidentalis) Transmits Maize Chlorotic Mottle Virus 总被引:2,自引:0,他引:2
Mingfu Zhao Honhing Ho Yixin Wu Yueqiu He Mengjiao Li 《Journal of Phytopathology》2014,162(7-8):532-536
Maize chlorotic mottle virus (MCMV) is one of the co‐infection pathogens that cause corn (maize) lethal necrosis, but the transmission mechanism of MCMV is not yet clear. In order to determine the ability of western flower thrips (Frankliniella occidentalis; WFT) to transmit MCMV, imported maize seeds from Thailand were germinated in an insect‐free greenhouse and the seedlings were tested for the transmission by WFT of chlorotic mottle virus disease. The thrips (WFT), starved for 48 h then allowed to feed for 30 min on maize plants infected with MCMV or asymptomatic maize plants, were transferred to healthy seedlings. After 35 days, the seedlings with WFT from diseased maize plants showed chlorotic mottle symptoms, whereas seedlings with WFT from asymptomatic maize plants remained healthy. A single band of 711 bp was amplified by RT‐PCR using primers MCMV‐F/MCMV‐R from the MCMV‐infected plants and WFT collected from the diseased plants. Sequencing of the amplified product and further sequence comparison indicated that the two viruses from both sources showed 99% similarity of nucleotides and they should be regarded as identical. In addition, isometric particles c. 30 nm in diameter, characteristic of MCMV, were found in the WFT samples from diseased maize plants. Thus, it is concluded that WFT transmits MCMV. Our findings suggest that corn lethal necrosis disease can be controlled or minimized by the eradication of WFT from the field or greenhouses. 相似文献
998.
Lei Yang Xudong Zhao Xianglong Tang 《International journal of biological sciences》2014,10(7):677-688
Network biology integrates different kinds of data, including physical or functional networks and disease gene sets, to interpret human disease. A clique (maximal complete subgraph) in a protein-protein interaction network is a topological module and possesses inherently biological significance. A disease-related clique possibly associates with complex diseases. Fully identifying disease components in a clique is conductive to uncovering disease mechanisms. This paper proposes an approach of predicting disease proteins based on cliques in a protein-protein interaction network. To tolerate false positive and negative interactions in protein networks, extending cliques and scoring predicted disease proteins with gene ontology terms are introduced to the clique-based method. Precisions of predicted disease proteins are verified by disease phenotypes and steadily keep to more than 95%. The predicted disease proteins associated with cliques can partly complement mapping between genotype and phenotype, and provide clues for understanding the pathogenesis of serious diseases. 相似文献
999.
Elina MS Paaso Maritta S Jaakkola Aino K Rantala Timo T Hugg Jouni JK Jaakkola 《Respiratory research》2014,15(1)
BackgroundFamily history of asthma and other allergic diseases have been linked to the risk of childhood asthma previously, but little is known about their effect on the age-of-onset and persistency of asthma until young adulthood.MethodsWe assessed the effect of the family history of asthma and allergic diseases on persistent vs. transient, and early- vs. late-onset persistent asthma in The Espoo Cohort Study 1991–2011, a population-based cohort study of 1623 subjects (follow-up rate 63.2%). The determinants were any family history (any parent or sibling); maternal; paternal; siblings only; parents only; and both siblings and parents. Analyses were conducted separately for asthma and allergic diseases while taking the other disease into account as a confounding factor. The outcomes were persistent, transient, early-onset persistent (<13 years) and late-onset persistent asthma. Adjusted risk ratios (RR) were calculated applying Poisson regression. Q-statistics were used to assess heterogeneity between RRs.ResultsFamily history was associated with the different subtypes but the magnitude of effect varied quantitatively. Any family history of asthma was a stronger determinant of persistent (adjusted RR = 2.82, 95% CI 1.99-4.00) than transient asthma (1.65, 1.03-2.65) (heterogeneity: P = 0.07) and on early-onset than late-onset persistent asthma. Also any family history of allergic diseases was a stronger determinant of persistent and early-onset asthma. The impact of paternal asthma continued to young adulthood (early-onset: 3.33, 1.57-7.06 vs. late-onset 2.04, 0.75-5.52) while the influence of maternal asthma decreased with age (Early-onset 3.94, 2.11-7.36 vs. Late-onset 0.88, 0.28-2.81). Paternal allergic diseases did not follow the pattern of paternal asthma, since they showed no association with late-onset asthma. Also the effect estimates for other subtypes were lower than in other hereditary groups (persistent 1.29, 0.75-2.22 vs. transient 1.20, 0.67-2.15 and early-onset 1.86, 0.95-3.64 vs. late-onset 0.64, 0.22-1.80).ConclusionsFamily history of asthma and allergic diseases are strong determinants of asthma, but the magnitude of effect varies according to the hereditary group so that some subtypes have a stronger hereditary component, and others may be more strongly related to environmental exposures. Our results provide useful information for assessing the prognosis of asthma based on a thorough family history. 相似文献
1000.
Hui Yang Natalia Volfovsky Alison Rattray Xiongfong Chen Hisashi Tanaka Jeffrey Strathern 《BMC genomics》2014,15(1)