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171.
Ellen?M?Unterwald Michelle?E?Page Timothy?B?Brown Jonathan?S?Miller Marta?Ruiz Karen?A?Pescatore Baoji?Xu Louis?French?Reichardt Joel?Beverley Bin?Tang Heinz?Steiner Elizabeth?A?Thomas Michelle?E?EhrlichEmail author 《Molecular neurodegeneration》2013,8(1):47
Background
The high affinity tyrosine kinase receptor, TrkB, is the primary receptor for brain derived neurotrophic factor (BDNF) and plays an important role in development, maintenance and plasticity of the striatal output medium size spiny neuron. The striatal BDNF/TrkB system is thereby implicated in many physiologic and pathophysiologic processes, the latter including mood disorders, addiction, and Huntington’s disease. We crossed a mouse harboring a transgene directing cre-recombinase expression primarily to postnatal, dorsal striatal medium spiny neurons, to a mouse containing a floxed TrkB allele (fB) mouse designed for deletion of TrkB to determine its role in the adult striatum.Results
We found that there were sexually dimorphic alterations in behaviors in response to stressful situations and drugs of abuse. Significant sex and/or genotype differences were found in the forced swim test of depression-like behaviors, anxiety-like behaviors on the elevated plus maze, and cocaine conditioned reward. Microarray analysis of dorsal striatum revealed significant dysregulation in individual and groups of genes that may contribute to the observed behavioral responses and in some cases, represent previously unidentified downstream targets of TrkB.Conclusions
The data point to a set of behaviors and changes in gene expression following postnatal deletion of TrkB in the dorsal striatum distinct from those in other brain regions.172.
173.
Summary A large number of projects have recently been initiated in Scotland aiming to restore native woodland, which are being undertaken by a variety of organisations, often in partnership, with environmental NGOs playing a leading role. The objectives, constraints and methodologies of these projects are critically reviewed, partly through a questionnaire survey. Most aim to restore ‘natural’ woodland, but the lack of appropriate reference ecosystems and uncertainty about the characteristics of the original forest hinder the development of precise objectives, and consequently the criteria for success are poorly defined. Most projects face major practical constraints, particularly browsing by herbivores and invasion by exotic species, indicating that they will require long-term management interventions. Most woodlands are isolated from other woodlands, which threatens their long-term viability, restricting colonisation by woodland organisms. Greater reference to ecological theory in practical restoration projects such as these would enable objectives to be defined with more precision, encourage a greater emphasis on ecological processes rather than community composition, and improve management plans through use of predictive tools. In particular, the integration of woodlands into habitat networks, increasing ecological connectivity between woodland fragments, is considered essential to ensure success in the long term. 相似文献
174.
Vicky Wang-Wei Tsai Laurence Macia Heiko Johnen Tamara Kuffner Rakesh Manadhar Sebastian Beck J?rgensen Ka Ki Michelle Lee-Ng Hong Ping Zhang Liyun Wu Christopher Peter Marquis Lele Jiang Yasmin Husaini Shu Lin Herbert Herzog David A. Brown Amanda Sainsbury Samuel N. Breit 《PloS one》2013,8(2)
The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1−/−) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1−/− mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1−/− mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage. 相似文献
175.
Laura N. Anderson Michelle Cotterchio Julia A. Knight Ayelet Borgida Steven Gallinger Sean P. Cleary 《PloS one》2013,8(6)
Recent studies of 25-hydroxyvitamin D (25(OH)D) levels and pancreas cancer have suggested a potential role of the vitamin D pathway in the etiology of this fatal disease. Variants in vitamin-D related genes are known to affect 25(OH)D levels and function and it is unknown if these variants may influence pancreatic cancer risk. The association between 87 single nucleotide polymorphisms (SNPs) in 11 genes was evaluated within the Ontario Pancreas Cancer Study, a population-based case-control study. Pancreatic cancer cases with pathology confirmed adenocarcinoma were identified from the Ontario Cancer Registry (n = 628) and controls were identified through random digit dialing (n = 1193). Age and sex adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated by multivariate logistic regression. SNPs in the CYP24A1, CYP2R1, calcium sensing receptor (CASR), vitamin D binding protein (GC), retinoid X receptor-alpha (RXRA) and megalin (LRP2) genes were significantly associated with pancreas cancer risk. For example, pancreas cancer risk was inversely associated with CYP2R1 rs10741657 (AA versus GG, OR = 0.70; 95%CI: 0.51–0.95) and positively with CYP24A1 rs6127119 (TT versus CC. OR = 1.94; 95%CI: 1.28–2.94). None of the associations were statistically significant after adjustment for multiple comparisons. Vitamin D pathway gene variants may be associated with pancreas cancer risk and future studies are needed to understand the possible role of vitamin D in tumorigenesis and may have implications for cancer-prevention strategies. 相似文献
176.
Gregory J. Tanner Michelle L. Colgrave Malcolm J. Blundell Hareshwar P. Goswami Crispin A. Howitt 《PloS one》2013,8(2)
Background
Subjects suffering from coeliac disease, gluten allergy/intolerance must adopt a lifelong avoidance of gluten. Beer contains trace levels of hordeins (gluten) which are too high to be safely consumed by most coeliacs. Accurate measurement of trace hordeins by ELISA is problematic.Methods
We have compared hordein levels in sixty beers, by sandwich ELISA, with the level determined using multiple reaction monitoring mass spectrometry (MRM-MS).Results
Hordein levels measured by ELISA varied by four orders of magnitude, from zero (for known gluten-free beers) to 47,000 µg/mL (ppm; for a wheat-based beer). Half the commercial gluten-free beers were free of hordein by MS and ELISA. Two gluten-free and two low-gluten beers had zero ELISA readings, but contained significant hordein levels (p<0.05), or near average (60–140%) hordein levels, by MS, respectively. Six beers gave false negatives, with zero ELISA readings but near average hordein content by MS. Approximately 20% of commercial beers had ELISA readings less than 1 ppm, but a near average hordein content by MS. Several barley beers also contained undeclared wheat proteins.Conclusions
ELISA results did not correlate with the relative content of hordein peptides determined by MS, with all barley based beers containing hordein. We suggest that mass spectrometry is more reliable than ELISA, as ELISA enumerates only the concentration of particular amino-acid epitopes; this may vary between different hordeins and may not be related to the absolute hordein concentration. MS quantification is undertaken using peptides that are specific and unique, enabling the quantification of individual hordein isoforms. This outlines the problem of relying solely on ELISA determination of gluten in beverages such as beer and highlights the need for the development of new sensitive and selective quantitative assay such as MS. 相似文献177.
Michelle A. Arya Albert K. Tai Eric C. Wooten Christopher D. Parkin Elena Kudryavtseva Gordon S. Huggins 《PloS one》2013,8(8)
The loss of muscle mass in alcoholic myopathy may reflect alcohol inhibition of myogenic cell differentiation into myotubes. Here, using a high content imaging system we show that ethanol inhibits C2C12 myoblast differentiation by reducing myogenic fusion, creating smaller and less complex myotubes compared with controls. Ethanol administration during C2C12 differentiation reduced MyoD and myogenin expression, and microarray analysis identified ethanol activation of the Notch signaling pathway target genes Hes1 and Hey1. A reporter plasmid regulated by the Hes1 proximal promoter was activated by alcohol treatment in C2C12 cells. Treatment of differentiating C2C12 cells with a gamma secretase inhibitor (GSI) abrogated induction of Hes1. On a morphological level GSI treatment completely rescued myogenic fusion defects and partially restored other myotube parameters in response to alcohol. We conclude that alcohol inhibits C2C12 myoblast differentiation and the inhibition of myogenic fusion is mediated by Notch pathway activation. 相似文献
178.
Jiannong Xu Julián F. Hillyer Boubacar Coulibaly Madjou Sacko Adama Dao Oumou Niaré Michelle M. Riehle Sekou F. Traoré Kenneth D. Vernick 《PloS one》2013,8(4)
Background
Malaria parasites undergo complex developmental transitions within the mosquito vector. A commonly used laboratory model for studies of mosquito-malaria interaction is the rodent parasite, P. berghei. Anopheles funestus is a major malaria vector in sub-Saharan Africa but has received less attention than the sympatric species, Anopheles gambiae. The imminent completion of the A. funestus genome sequence will provide currently lacking molecular tools to describe malaria parasite interactions in this mosquito, but previous reports suggested that A. funestus is not permissive for P. berghei development.Methods
An A. funestus population was generated in the laboratory by capturing female wild mosquitoes in Mali, allowing them to oviposit, and rearing the eggs to adults. These F1 progeny of wild mosquitoes were allowed to feed on mice infected with a fluorescent P. berghei strain. Fluorescence microscopy was used to track parasite development inside the mosquito, salivary gland sporozoites were tested for infectivity to mice, and parasite development in A. funestus was compared to A. gambiae.Results
P. berghei oocysts were detectable on A. funestus midguts by 7 days post-infection. By 18–20 days post-infection, sporozoites had invaded the median and distal lateral lobes of the salivary glands, and hemocoel sporozoites were observed in the hemolymph. Mosquitoes were capable of infecting mice via bite, demonstrating that A. funestus supports the complete life cycle of P. berghei. In a random sample of wild mosquito genotypes, A. funestus prevalence of infection and the characteristics of parasite development were similar to that observed in A. gambiae-P. berghei infections.Conclusions
The data presented in this study establish an experimental laboratory model for Plasmodium infection of A. funestus, an important vector of human malaria. Studying A. funestus-Plasmodium interactions is now feasible in a laboratory setting. This information lays the groundwork for exploitation of the awaited genome sequence of A. funestus. 相似文献179.
180.
David P. Dimmock Michelle M. Clark Mary Gaughran Julie A. Cakici Sara A. Caylor Christina Clarke Michele Feddock Shimul Chowdhury Lisa Salz Cynthia Cheung Lynne M. Bird Charlotte Hobbs Kristen Wigby Lauge Farnaes Cinnamon S. Bloss Stephen F. Kingsmore the RCIGM Investigators 《American journal of human genetics》2020,107(5):942