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991.
Tian E Ten Hagen KG Shum L Hang HC Imbert Y Young WW Bertozzi CR Tabak LA 《The Journal of biological chemistry》2004,279(48):50382-50390
The family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (ppGaNTases) is responsible for initiating mucin-type O-linked glycosylation in higher eukaryotes. To begin to examine the biological role of O-linked glycosylation, mammalian cells were treated with a small molecule inhibitor (designated 1-68A, Ref. 15) of ppGaNTase activity. NIH3T3 cells exposed to the inhibitor were shown to undergo a significant reduction in cell surface O-glycosylation as detected by staining with jacalin and peanut agglutinin lectins after 30 min of treatment; no reduction in staining using antibodies to O-linked N-acetylglucosamine or the lectin concanavalin A was detected. Apoptosis was also observed in treated cells after 45 min of exposure, ostensibly following the O-glycosylation reduction. Overexpression of several different ppGaNTase isoforms restored cell surface O-glycosylation and rescued inhibitor-induced apoptosis. Additionally, mouse embryonic mandibular organ cultures exposed to 1-68A developed abnormally, presumably because of epithelial and mesenchymal apoptosis that followed a reduction in jacalin and peanut agglutinin staining. Our studies suggest that mucin-type O-linked glycosylation may be required for normal development and that ppGaNTases may play a role in the regulation of apoptosis. 相似文献
992.
A standardized kinesin nomenclature 总被引:28,自引:0,他引:28
Lawrence CJ Dawe RK Christie KR Cleveland DW Dawson SC Endow SA Goldstein LS Goodson HV Hirokawa N Howard J Malmberg RL McIntosh JR Miki H Mitchison TJ Okada Y Reddy AS Saxton WM Schliwa M Scholey JM Vale RD Walczak CE Wordeman L 《The Journal of cell biology》2004,167(1):19-22
In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered. 相似文献
993.
Food, water, and worker protection regulations have driven availability, and loss, of pesticides for use in pest management programs. In response, public-supported research and extension projects have targeted investigation and demonstration of reduced-risk integrated pest management (IPM) techniques. But these new techniques often result in higher financial burden to the grower, which is counter to the IPM principle that economic competitiveness is critical to have IPM adopted. As authorized by the 2002 Farm Bill and administered by the U.S. Department of Agriculture (USDA) Natural Resources Conservation Service (NRCS), conservation programs exist for delivering public-supported financial incentives to growers to increase environmental stewardship on lands in production. NRCS conservation programs are described, and the case for providing financial incentives to growers for implementing IPM is presented. We also explored the opportunity and challenge to use one key program, the Environmental Quality Incentives Program (EQIP), to aid grower adoption of IPM. The EQIP fund distribution to growers from 1997 to 2002 during the last Farm Bill cycle totaled approximately 1.05 billion dollars with a portion of funds supporting an NRCS-designed pest management practice. The average percentage of allocation of EQIP funds to this pest management practice among states was 0.77 +/- 0.009% (mean +/- SD). Using Michigan as an example, vegetable and fruit grower recognition of the program's use to implement IPM was modest (25% of growers surveyed), and their recognition of its use in aiding implementation of IPM was improved after educational efforts (74%). Proposals designed to enhance program usefulness in implementing IPM were delivered through the NRCS advisory process in Michigan. Modifications for using the NRCS pest management practice to address resource concerns were adopted, incentive rates for pest management were adjusted, and an expanded incentive structure for IPM technique adoption was tabled for future consideration. The case is strong for using public-supported financial incentives offered by the EQIP to aid grower adoption of IPM as a means to address resource concerns, but current use of the EQIP for this purpose is modest to meager. With appropriate program adjustments and increased grower awareness, USDA NRCS conservation programs, and the EQIP in particular, may provide an important opportunity for growers to increase their use of IPM as a resource conservation and farm management tool. 相似文献
994.
995.
Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis 总被引:3,自引:0,他引:3
Fontoura P Ho PP DeVoss J Zheng B Lee BJ Kidd BA Garren H Sobel RA Robinson WH Tessier-Lavigne M Steinman L 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(11):6981-6992
Nogo-66, the extracellular 66 aa loop of the Nogo-A protein found in CNS myelin, interacts with the Nogo receptor and has been proposed to mediate inhibition of axonal regrowth. It has been shown that immunization with Nogo-A promotes recovery in animal models of spinal cord injury through induction of Ab production. In this report, studies were performed to characterize the immune response to Nogo-66 and to determine the role of Nogo in experimental autoimmune encephalomyelitis (EAE). Immunization of EAE-susceptible mouse strains with peptides derived from Nogo-66 induced a CNS immune response with clinical and pathological similarities to EAE. The Nogo-66 peptides elicited strong T cell responses that were not cross-reactive to other encephalitogenic myelin Ags. Using a large scale spotted microarray containing proteins and peptides derived from a wide spectrum of myelin components, we demonstrated that Nogo-66 peptides also generated a specific Ab response that spreads to several other encephalitogenic myelin Ags following immunization. Nogo-66-specific T cell lines ameliorated established EAE, via Nogo-66-specific Th2 cells that entered the CNS. These results indicate that some T cell and B cell immune responses to Nogo-66 are associated with suppression of ongoing EAE, whereas other Nogo-66 epitopes can be encephalitogenic. 相似文献
996.
Agius LM 《Journal of theoretical biology》2004,227(2):219-228
Within a framework of dual involvement of mucosa and submucosa on the one hand, and of the muscularis propria of the bowel wall on the other, it might be valid to consider involvement of the vascular supply as the essential means in itself of not only causing the morphologic lesions in inflammatory bowel disease, but also especially in accounting for persisting patterns of inflammatory response both in ulcerative colitis and in Crohn's disease. Inflammatory bowel disease as a group constitutes a spectrum of biologic and pathobiologic manifestations in terms not only of inflammatory involvement of the bowel wall but also in terms of how the bowel in its turn deals with inflammation as a pathologic lesion in its own right. Parameters of inflammatory bowel activity transcend simple concepts of etiology and pathogenesis as applicable to category disorders such as infections or bowel ischemia. Indeed, the strictly characterized initiation of the inflammatory bowel response as a function of defective regulation of the antigenicity of the luminal contents on the one hand, and on interactions between nitric oxide and free oxygen radicals on the other, might help determine a persistence of tissue damage in inflammatory bowel disease that is either relapsing/remitting or chronic in progression. In a final analysis, perhaps, there might be involved a single central form of pathway induction of dysregulated immune reactivity arising from an early disturbance in activation patterns as induced by the onset of luminal antigenicity at an early or specific-stage, further characterized perhaps by specific forms of intestinal epithelial defects of the bowel mucosa in patients subsequently developing inflammatory bowel disease. Specific genetic markers for disease susceptibility and for therapeutic responsiveness are particularly of interest. The Nucleotide binding oligomerization Domain 2 (NOD2) would recognize microbial lipopolysaccharide or else mark systemic responses to pathogens that are pathogenic to evolving inflammatory bowel disease. 相似文献
997.
998.
(3)H]Adenosine uptake in brainstem membranes of CD-1 mice lacking the adenosine A(2a) receptor 总被引:1,自引:0,他引:1
Previous studies in our laboratory have demonstrated a decrease in [(3)H]nitrobenzylthioinosine binding sites in the brainstem of adenosine A(2a) receptor knockout mice, particularly in the brain nuclei involved in central control of cardiovascular function [Brain Research 877 (2000) 160]. The present study aimed to correlate this decrease, shown using autoradiography, with a functional change using a previously described method of [(3)H]adenosine uptake in a membrane preparation from the brainstem of wildtype CD - 1 and homozygous mutant mice lacking the adenosine A(2a) receptor. A statistically significant decrease was shown in the mean V(MAX) value obtained from homozygous mutant preparations (4.7 +/- 1.3 fmol/mg protein/20 s, P < 0.05, n = 4) compared to that obtained from wildtype controls (51.6 +/- 4.2 fmol/mg protein/20 s, n = 4). Competition studies using nucleoside uptake inhibitors showed a statistically significant increase in the log IC(50) values for dipyridamole (Wildtype: -4.3 +/- 0.2, Homozygous mutant: -8.3 +/- 0.4, n=5, P < 0.05) and dilazep (Wildtype: -3.9 +/- 0.8, Homozygous mutant: -8.3 +/- 0.8, n=5, P < 0.05) in the preparations using homozygous mutant tissue. The present study, in conjunction with the results of previous studies [Brain Research 877 (2000) 160], indicates that components of purinergic neurotransmission system have apparently adjusted in compensation for the lack of the A(2a) receptor. 相似文献
999.
Saunders MA Good JM Lawrence EC Ferrell RE Li WH Nachman MW 《American journal of human genetics》2006,79(6):1089-1097
Myostatin (GDF8) is a negative regulator of muscle growth in mammals, and loss-of-function mutations are associated with increased skeletal-muscle mass in mice, cattle, and humans. Here, we show that positive natural selection has acted on human nucleotide variation at GDF8, since the observed ratio of nonsynonymous:synonymous changes among humans is significantly greater than expected under the neutral model and is strikingly different from patterns observed across mammalian orders. Furthermore, extended haplotypes around GDF8 suggest that two amino acid variants have been subject to recent positive selection. Both mutations are rare among non-Africans yet are at frequencies of up to 31% in sub-Saharan Africans. These signatures of selection at the molecular level suggest that human variation at GDF8 is associated with functional differences. 相似文献
1000.
Schnackenberg BJ Jones SM Pate C Shank B Sessions L Pittman LM Cornett LE Kurten RC 《American journal of physiology. Lung cellular and molecular physiology》2006,290(3):L485-L491
Asthma is a disease characterized by reversible airway obstruction. An additional hallmark of chronic asthma is altered wound healing that leads to airway remodeling. Although beta-agonists are effective in treating the bronchospasm associated with asthma, their effects on airway wound healing, which are related to airway remodeling, are unknown. It has been demonstrated that beta-agonists can alter the signaling of epidermal growth factor (EGF) receptors, which are important in timely wound healing. Therefore, we hypothesized that the beta-agonist isoproterenol would affect wound healing. Using an in vitro scrape wound assay, we demonstrated that isoproterenol attenuates EGF-stimulated wound healing in 16HBE airway epithelial cell cultures. Through experiments with forskolin and cells overexpressing beta2-adrenergic receptor-yellow fluorescent protein, we show that attenuation is due to the accumulation of cAMP and the involvement of at least one additional pathway. Furthermore, attenuation is not due to a direct effect on the EGF receptor or to an alteration of the ERK/MAPK signaling cascade. Based on these results, we propose that isoproterenol may exert its effects through other MAPK signaling pathways (JNK and/or p38) or through parallel mechanisms. These results also demonstrate a problem of potential therapeutic relevance in which a commonly prescribed medication may alter wound healing and contribute to the remodeling of asthmatic airways. 相似文献