全文获取类型
收费全文 | 4076篇 |
免费 | 262篇 |
国内免费 | 2篇 |
出版年
2023年 | 17篇 |
2022年 | 48篇 |
2021年 | 99篇 |
2020年 | 59篇 |
2019年 | 71篇 |
2018年 | 101篇 |
2017年 | 93篇 |
2016年 | 133篇 |
2015年 | 217篇 |
2014年 | 198篇 |
2013年 | 284篇 |
2012年 | 340篇 |
2011年 | 363篇 |
2010年 | 219篇 |
2009年 | 183篇 |
2008年 | 250篇 |
2007年 | 244篇 |
2006年 | 209篇 |
2005年 | 208篇 |
2004年 | 175篇 |
2003年 | 173篇 |
2002年 | 148篇 |
2001年 | 38篇 |
2000年 | 33篇 |
1999年 | 24篇 |
1998年 | 34篇 |
1997年 | 31篇 |
1996年 | 23篇 |
1995年 | 25篇 |
1994年 | 19篇 |
1993年 | 30篇 |
1992年 | 17篇 |
1991年 | 10篇 |
1990年 | 16篇 |
1989年 | 14篇 |
1988年 | 8篇 |
1987年 | 11篇 |
1986年 | 12篇 |
1985年 | 12篇 |
1984年 | 16篇 |
1983年 | 11篇 |
1982年 | 17篇 |
1981年 | 6篇 |
1980年 | 12篇 |
1979年 | 9篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 16篇 |
1966年 | 5篇 |
排序方式: 共有4340条查询结果,搜索用时 125 毫秒
71.
Hydrobiologia - Mussels provide important ecological functions in freshwater ecosystems but the associations between Amazonian mussels, macroinvertebrate assemblage and habitat quality remain... 相似文献
72.
Jennifer C. Erasmus Kasia Smolarczyk Helena Brezovjakova Noor F. Mohd-Naim Encarnacin Lozano Karl Matter Vania M.M. Braga 《The Journal of cell biology》2021,220(6)
Rac1 GTPase is hyperactivated in tumors and contributes to malignancy. Rac1 disruption of junctions requires its effector PAK1, but the precise mechanisms are unknown. Here, we show that E-cadherin is internalized via micropinocytosis in a PAK1–dependent manner without catenin dissociation and degradation. In addition to internalization, PAK1 regulates E-cadherin transport by fine-tuning Rab small GTPase function. PAK1 phosphorylates a core Rab regulator, RabGDIβ, but not RabGDIα. Phosphorylated RabGDIβ preferentially associates with Rab5 and Rab11, which is predicted to promote Rab retrieval from membranes. Consistent with this hypothesis, Rab11 is activated by Rac1, and inhibition of Rab11 function partially rescues E-cadherin destabilization. Thus, Rac1 activation reduces surface cadherin levels as a net result of higher bulk flow of membrane uptake that counteracts Rab11-dependent E-cadherin delivery to junctions (recycling and/or exocytosis). This unique small GTPase crosstalk has an impact on Rac1 and PAK1 regulation of membrane remodeling during epithelial dedifferentiation, adhesion, and motility. 相似文献
73.
Zucaratto Rodrigo Santos Pires Alexandra Godoy Bergallo Helena Portela Rita de Cássia Quitete 《Plant Ecology》2021,222(1):93-105
Plant Ecology - Population models are helpful for understanding demographic trends in invasive plants and crucial in defining effective management actions. Here, we assessed the dynamics of three... 相似文献
74.
Woyneshet Gelaye Nana Aba Williams Stella Kepha Augusto Messa Junior Pedro Emanuel Fleitas Helena Marti-Soler Destaw Damtie Sissay Menkir Alejandro J. Krolewiecki Lisette van Lieshout Wendemagegn Enbiale 《PLoS neglected tropical diseases》2021,15(2)
BackgroundSoil-transmitted helminths (STH) are common in low and middle income countries where there is lack of access to clean water and sanitation. Effective diagnosis and treatment are essential for the control of STH infections. However, among STH parasites, Strongyloides stercoralis is the most neglected species, both in diagnostics and control strategies. Diagnostic methods cover different approaches, each with different sensitivities and specificities, such as serology, molecular techniques and microscopy based techniques. Of the later, the Baermann technique is the most commonly used procedure. In the literature, several ways have been described to perform the Baermann method, which illustrates the overall lack of a ‘(gold) reference standard’ method for the diagnosis of S. stercoralis infection. In this study we have evaluated the performance of three Baermann techniques in order to improve the reference standard for the microscopic diagnosis of S. stercoralis infection thereby facilitating individual case detection, mapping of the disease and proper evaluation of treatment responses.Methods/Principal findingsA community based cross sectional study was conducted at Zenzelima, Bahir Dar Zuria Ethiopia. A total of 437 stool samples were collected and analyzed by the following procedures: conventional Baermann (CB), modified Baermann (MB), and modified Baermann with charcoal pre-incubation (MBCI). The diagnostic sensitivity and Negative Predictive Value (NPV) of each technique was calculated using the combination of all the three techniques as a composite reference standard. Our result indicated that larvae of S. stercoralis were detected in 151 (34.6%) stool samples. The prevalence of S. stercoralis infection based on the three diagnostic methods was 9.6%, 8.0%, and 31.3% by CB, MB, and MBCI respectively. The sensitivity and NPV for CB, MB, and MBCI were 26.7% and 70.8%, 22.1% and 69.6%, and 87.0% and 93.2%, respectively. The MBCI showed significant difference (P- value = <0.001) in the sensitivity and NPV values when compared with CB and MB values. The agreement between CB, MB, and MBCI with the composite reference standard was 31.8%, 26.7%, 89.6%, respectively.Conclusion/SignificanceOur results suggest the superior performance of MBCI. It is relatively easy to implement, simple to perform and comparatively cheaper. The CB is by far the commonly used method in routine diagnostic although this technique significantly underestimates the true burden of the disease and thereby contributing to the exclusion of S. stercoralis from the control strategies. Therefore, MBCI is recommended as a routine microscopy-based diagnostic test for S. stercoralis infection, particularly in settings where molecular procedures are not available. 相似文献
75.
Lezaan Prinsloo Alex Naidoo June Serem Helena Taute Yasien Sayed Megan Bester Albert Neitz Anabella Gaspar 《Journal of peptide science》2013,19(5):325-332
Tick defensins may serve as templates for the development of multifunctional peptides. The purpose of this study was to evaluate shorter peptides derived from tick defensin isoform 2 (OsDef2) in terms of their antibacterial, antioxidant, and cytotoxic activities. We compared the structural and functional properties of a synthetic peptide derived from the carboxy‐terminal of the parent peptide (Os) to that of an analogue in which the three cysteine residues were omitted (Os–C). Here, we report that both peptides were bactericidal (MBC values ranging from 0.94–15 µg/ml) to both Gram‐positive and Gram‐negative bacteria, whereas the parent peptide only exhibited Gram‐positive antibacterial activity. The Os peptide was found to be two‐fold more active than Os–C against three of the four tested bacteria but equally active against Staphylococcus aureus. Os showed rapid killing kinetics against both Escherichia coli and Bacillus subtilis, whereas Os–C took longer, suggesting different modes of action. Scanning electron microscopy showed that in contrast to melittin for which blebbing of bacterial surfaces was observed, cells exposed to either peptide appeared flattened and empty. Circular dichroism data indicated that in a membrane‐mimicking environment, the cysteine‐containing peptide has a higher α‐helical content. Both peptides were found to be non‐toxic to mammalian cells. Moreover, the peptides displayed potent antioxidant activity and were 12 times more active than melittin. Multifunctional peptides hold potential for a wide range of clinical applications and further investigation into their mode of antibacterial and antioxidant properties is therefore warranted. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
76.
Filipe O. Costa Teresa Neuparth M. Helena Costa Christopher W. Theodorakis Lee R. Shugart 《Biomarkers》2013,18(6):451-463
This article describes the leading steps to develop an assay of DNA damage for the marine amphipod Gammarus locusta, using agarose gel electrophoresis (AGE). To test the sensitivity and feasibility of the AGE technique, X-ray assays were performed with naked DNA and with live amphipods. These positive controls demonstrated the effectiveness of the AGE technique to not only discriminate distinct levels of DNA strand breakage in a dose-dependent manner, but also to identify and quantify the type of strand breakage induced. It was also shown that it is possible to detect DNA damage using whole-body DNA extracts from amphipods. To explore the potential of this technique for use in ecotoxicological studies with amphipods, a 96-h waterborne-copper toxicity test was performed. Copper-induced DNA strand breakage was first observed after 24 h of exposure, and was recorded again at 96 h, at a copper concentration of 20 μg l -1 . The absence of strand breakage after 48 h of exposure is discussed in the light of the underlying mechanisms of copper toxicity and DNA repair. These studies demonstrated the feasibility of including DNA damage as a biomarker in ecotoxicological studies with amphipods. Information gained from the use of this biomarker would help with the interpretation of chronic toxicity tests and would contribute to our understanding of the impact of genotoxic insult in marine invertebrates, particularly crustaceans. 相似文献
77.
78.
79.
Jonathan D. Mosley Sara L. Van Driest Emma K. Larkin Peter E. Weeke John S. Witte Quinn S. Wells Jason H. Karnes Yan Guo Lisa Bastarache Lana M. Olson Catherine A. McCarty Jennifer A. Pacheco Gail P. Jarvik David S. Carrell Eric B. Larson David R. Crosslin Iftikhar J. Kullo Gerard Tromp Helena Kuivaniemi David J. Carey Marylyn D. Ritchie Josh C. Denny Dan M. Roden 《PloS one》2013,8(12)
A single mutation can alter cellular and global homeostatic mechanisms and give rise to multiple clinical diseases. We hypothesized that these disease mechanisms could be identified using low minor allele frequency (MAF<0.1) non-synonymous SNPs (nsSNPs) associated with “mechanistic phenotypes”, comprised of collections of related diagnoses. We studied two mechanistic phenotypes: (1) thrombosis, evaluated in a population of 1,655 African Americans; and (2) four groupings of cancer diagnoses, evaluated in 3,009 white European Americans. We tested associations between nsSNPs represented on GWAS platforms and mechanistic phenotypes ascertained from electronic medical records (EMRs), and sought enrichment in functional ontologies across the top-ranked associations. We used a two-step analytic approach whereby nsSNPs were first sorted by the strength of their association with a phenotype. We tested associations using two reverse genetic models and standard additive and recessive models. In the second step, we employed a hypothesis-free ontological enrichment analysis using the sorted nsSNPs to identify functional mechanisms underlying the diagnoses comprising the mechanistic phenotypes. The thrombosis phenotype was solely associated with ontologies related to blood coagulation (Fisher''s p = 0.0001, FDR p = 0.03), driven by the F5, P2RY12 and F2RL2 genes. For the cancer phenotypes, the reverse genetics models were enriched in DNA repair functions (p = 2×10−5, FDR p = 0.03) (POLG/FANCI, SLX4/FANCP, XRCC1, BRCA1, FANCA, CHD1L) while the additive model showed enrichment related to chromatid segregation (p = 4×10−6, FDR p = 0.005) (KIF25, PINX1). We were able to replicate nsSNP associations for POLG/FANCI, BRCA1, FANCA and CHD1L in independent data sets. Mechanism-oriented phenotyping using collections of EMR-derived diagnoses can elucidate fundamental disease mechanisms. 相似文献