全文获取类型
收费全文 | 3287篇 |
免费 | 194篇 |
专业分类
3481篇 |
出版年
2024年 | 2篇 |
2023年 | 19篇 |
2022年 | 44篇 |
2021年 | 95篇 |
2020年 | 41篇 |
2019年 | 75篇 |
2018年 | 110篇 |
2017年 | 116篇 |
2016年 | 166篇 |
2015年 | 170篇 |
2014年 | 222篇 |
2013年 | 246篇 |
2012年 | 292篇 |
2011年 | 305篇 |
2010年 | 199篇 |
2009年 | 115篇 |
2008年 | 222篇 |
2007年 | 191篇 |
2006年 | 157篇 |
2005年 | 182篇 |
2004年 | 117篇 |
2003年 | 128篇 |
2002年 | 86篇 |
2001年 | 16篇 |
2000年 | 11篇 |
1999年 | 15篇 |
1998年 | 17篇 |
1997年 | 15篇 |
1996年 | 5篇 |
1995年 | 14篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1985年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1967年 | 1篇 |
1957年 | 1篇 |
1955年 | 1篇 |
1954年 | 2篇 |
1948年 | 1篇 |
1945年 | 1篇 |
排序方式: 共有3481条查询结果,搜索用时 15 毫秒
71.
Bielas SL Serneo FF Chechlacz M Deerinck TJ Perkins GA Allen PB Ellisman MH Gleeson JG 《Cell》2007,129(3):579-591
The axonal shafts of neurons contain bundled microtubules, whereas extending growth cones contain unbundled microtubule filaments, suggesting that localized activation of microtubule-associated proteins (MAP) at the transition zone may bundle these filaments during axonal growth. Dephosphorylation is thought to lead to MAP activation, but specific molecular pathways have remained elusive. We find that Spinophilin, a Protein-phosphatase 1 (PP1) targeting protein, is responsible for the dephosphorylation of the MAP Doublecortin (Dcx) Ser 297 selectively at the "wrist" of growing axons, leading to activation. Loss of activity at the "wrist" is evident as an impaired microtubule cytoskeleton along the shaft. These findings suggest that spatially restricted adaptor-specific MAP reactivation through dephosphorylation is important in organization of the neuronal cytoskeleton. 相似文献
72.
Laska MJ Strandbygård D Kjeldgaard A Mains M Corydon TJ Memon AA Sørensen BS Vogel U Jensen UB Nexø BA 《Experimental cell research》2007,313(12):2611-2621
The RAI gene is also known as iASPP and PPP1R13L. Recent investigations have shown that the region encompassing RAI is important for the development of cancer in young and middle-aged persons. It has been speculated that the RAI product induces apoptosis by blocking NF-kappaB or inhibits apoptosis by blocking p53. Either way the gene could influence the survival of precancerous lesions. Here we report that the expression of RAI mRNA was increased in non-transformed lymphocytes and fibroblasts induced to undergo apoptosis by various means, such as treatment with etoposide, calcium ions, or interleukin-2 and/or serum deprivation. Treatment with etoposide increased the content of RAI protein, too, and caused it to translocate to the nucleus. Inhibition of RAI expression in lymphocytes and fibroblasts with siRNA reduced apoptosis, but treatment with the NF-kappaB-inhibiting substance sulfasalazine relieved this dependence. In the transformed cell line HEK-293 the association between RAI induction and apoptosis seemed broken. Thus, we hypothesize that RAI induction is necessary but not sufficient for apoptosis induction in non-transformed cells. Our results could be explained by a NF-kappaB mediated mechanism. 相似文献
73.
Nexø BA Christensen T Frederiksen J Møller-Larsen A Oturai AB Villesen P Hansen B Nissen KK Laska MJ Petersen TS Bonnesen S Hedemand A Wu T Wang X Zhang X Brudek T Maric R Søndergaard HB Sellebjerg F Brusgaard K Kjeldbjerg AL Rasmussen HB Nielsen AL Nyegaard M Petersen T Børglum AD Pedersen FS 《PloS one》2011,6(2):e16652
We have investigated the role of human endogenous retroviruses in multiple sclerosis by analyzing the DNA of patients and controls in 4 cohorts for associations between multiple sclerosis and polymorphisms near viral restriction genes or near endogenous retroviral loci with one or more intact or almost-intact genes. We found that SNPs in the gene TRIM5 were inversely correlated with disease. Conversely, SNPs around one retroviral locus, HERV-Fc1, showed a highly significant association with disease. The latter association was limited to a narrow region that contains no other known genes. We conclude that HERV-Fc1 and TRIM5 play a role in the etiology of multiple sclerosis. If these results are confirmed, they point to new modes of treatment for multiple sclerosis. 相似文献
74.
75.
Dabu B Mironiuc-Cureu M Jardan D Szmal C 《Roumanian archives of microbiology and immunology》2011,70(4):145-148
Treponema denticola has been associated with gingivitis and chronic periodontitis. The aim of this study was to identify Treponema denticola in subgingival samples using PCR technology and to correlate it with clinical diagnosis of subjects. The study was carried out on seventy patients (20-84 years of age; mean age, 45.06 +/- 12.58) of which 22 individuals with no detectable gingivitis or periodontitis, 4 subjects with chronic gingivitis and 44 subjects with chronic periodontitis. Subgingival plaque samples were collected from five sites in each patient. DNA was extracted from the samples using QIAamp DNA Mini Kit (QIAGEN). Treponema denticola and other four periodontopathogens were found using multiplex polymerase chain reaction followed by a reverse hybridization. The relationship between clinical diagnoses and detection of Treponema denticola was determined with Fisher exact test. The results showed significant differences between diagnostic groups regarding subject proportion. Treponema denticola was detected in 2 out of 22 subjects with no detectable gingivitis or periodontitis, 2 out of 4 subjects with chronic gingivitis, and 40 out of 44 subjects with chronic periodontitis. Our findings suggest that Treponema denticola is closely connected to the initiation and progression of periodontal disease. 相似文献
76.
Almeida J Quadrana L Asís R Setta N de Godoy F Bermúdez L Otaiza SN Corrêa da Silva JV Fernie AR Carrari F Rossi M 《Journal of experimental botany》2011,62(11):3781-3798
Vegetables are critical for human health as they are a source of multiple vitamins including vitamin E (VTE). In plants, the synthesis of VTE compounds, tocopherol and tocotrienol, derives from precursors of the shikimate and methylerythritol phosphate pathways. Quantitative trait loci (QTL) for α-tocopherol content in ripe fruit have previously been determined in an Solanum pennellii tomato introgression line population. In this work, variations of tocopherol isoforms (α, β, γ, and δ) in ripe fruits of these lines were studied. In parallel all tomato genes structurally associated with VTE biosynthesis were identified and mapped. Previously identified VTE QTL on chromosomes 6 and 9 were confirmed whilst novel ones were identified on chromosomes 7 and 8. Integrated analysis at the metabolic, genetic and genomic levels allowed us to propose 16 candidate loci putatively affecting tocopherol content in tomato. A comparative analysis revealed polymorphisms at nucleotide and amino acid levels between Solanum lycopersicum and S. pennellii candidate alleles. Moreover, evolutionary analyses showed the presence of codons evolving under both neutral and positive selection, which may explain the phenotypic differences between species. These data represent an important step in understanding the genetic determinants of VTE natural variation in tomato fruit and as such in the ability to improve the content of this important nutriceutical. 相似文献
77.
Angela Dawson Nguyen-Toan Tran Elizabeth Westley Viviana Mangiaterra Mario Festin 《PloS one》2014,9(10)
Objectives
Emergency contraception pills (ECP) are among the 13 essential commodities in the framework for action established by the UN Commission on Life-Saving Commodities for Women and Children. Despite having been on the market for nearly 20 years, a number of barriers still limit women''s access to ECP in low- and middle-income countries (LMIC) including limited consumer knowledge and poor availability. This paper reports the results of a review to synthesise the current evidence on service delivery strategies to improve access to ECP.Methods
A narrative synthesis methodology was used to examine peer reviewed research literature (2003 to 2013) from diverse methodological traditions to provide critical insights into strategies to improve access from a service delivery perspective. The studies were appraised using established scoring systems and the findings of included papers thematically analysed and patterns mapped across all findings using concept mapping.Findings
Ten papers were included in the review. Despite limited research of adequate quality, promising strategies to improve access were identified including: advance provision of ECP; task shifting and sharing; intersectoral collaboration for sexual assault; m-health for information provision; and scale up through national family planning programs.Conclusion
There are a number of gaps in the research concerning service delivery and ECP in LMIC. These include a lack of knowledge concerning private/commercial sector contributions to improving access, the needs of vulnerable groups of women, approaches to enhancing intersectoral collaboration, evidence for social marketing models and investment cases for ECP. 相似文献78.
79.
Magdalena Kanabus Adrianna Nowicka Ewa Sledziewska-Gójska Piotr Jonczyk Zygmunt Ciesla 《Molecular & general genetics : MGG》1995,247(2):216-221
It has previously been suggested that inhibition of the proofreading 3-5 exonuclease activity of DNA polymerase may play an important role in generation of UV-induced mutations inEscherichia coli. Our previous work showing that overproduction of , the proofreading subunit of DNA polymerase III, counteracts the SOS mutagenic response ofE. coli seemed to be consistent with this hypothesis. To explore further the nature of the antimutagenic effect of we constructed plasmid pMK17, which encodes only two of the three highly conserved segments of — Exol and ExoII; the third segment, ExoIII, which is essential for 3–5 exonuclease activity, is deleted. We show that at 40°C, over-production of the truncated e subunit significantly delays production of M13 phage, suggesting that the protein retains its capacity to bind to DNA. On the other hand, the presence of pMK17 in atrpE65 strain growing at 40°C causes a 10-fold decrease in the frequency of UV-induced Trp+ mutations. This antimutagenic effect of the truncated s is effectively relieved by excess UmuD,C proteins. We also show that the presence of plasmid pIP21, which contains thednaQ49 allele encoding an subunit that is defective in proofreading activity, almost completely prevents generation of UV-induced mutations in thetrpE65 strain. We propose that the DNA binding ability of free , rather than its 3–5 exonuclease activity, affects processing of premutagenic UV-induced lesions, possibly by interfering with the interaction between the UmuC-UmuD-RecA complex and Pol III holoenzyme. This interaction is probably a necessary condition for translesion synthesis. 相似文献
80.
Kurowska M Rudnicka W Kontny E Janicka I Chorazy M Kowalczewski J Ziółkowska M Ferrari-Lacraz S Strom TB Maśliński W 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(4):1760-1767
The hallmarks of rheumatoid arthritis (RA) are leukocytic infiltration of the synovium and expansiveness of fibroblast-like synoviocytes (FLS). The abnormal proliferation of FLS and their resistance to apoptosis is mediated, at least in part, by present in RA joints proinflammatory cytokines and growth factors. Because IL-15 exerts properties of antiapoptotic and growth factors, and is produced by RA FLS, we hypothesized that IL-15 participates in RA FLS activation. To test this hypothesis, we first examined whether RA FLS express chains required for high affinity functional IL-15R. Indeed, RA FLS express IL-15Ralpha at mRNA and protein levels. Moreover, we confirmed the presence of IL-2Rbeta and common gamma-chains. Interestingly, TNF-alpha or IL-1beta triggered significant elevation of IL-15Ralpha chain at mRNA and protein levels. Next, we investigated the effects of exogenous or endogenous IL-15 on Bcl-2 and Bcl-x(L) expression, FLS proliferation, and apoptosis. Exogenous IL-15 enhanced RA FLS proliferation and increased the level of mRNA-encoding Bcl-x(L). To test the role of endogenous IL-15 in the activation of RA FLS, an IL-15 mutant/Fcgamma2a protein exerting properties of specific antagonist to the IL-15Ralpha chain was used. We found that blocking IL-15 biological activities using this protein substantially reduced endogenous expression of Bcl-2 and Bcl-x(L), and RA FLS proliferation that was reflected by increased apoptosis. Thus, we have demonstrated that a distinctive phenotype of RA FLS, i.e., persistent activation, proliferation, and resistance to apoptosis, is related to the autocrine activation of IL-15Rs by FLS-derived IL-15. 相似文献