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Genetic analysis of inbreeding of two strains of the parasitic nematode Haemonchus contortus 总被引:1,自引:0,他引:1
Roos MH Otsen M Hoekstra R Veenstra JG Lenstra JA 《International journal for parasitology》2004,34(1):109-115
Haemonchus contortus is a sheep parasitic nematode that causes severe economic losses. Previous studies have indicated a high degree of genetic heterogeneity, which is hardly affected by selection for drug resistance. As a tool for the analysis of the population dynamics of H. contortus and its response to drug resistance, we designed a strategy to study the inbreeding of a benzimidazole-sensitive and a benzimidazole-resistant strain. After 15 generations, a theoretical inbreeding coefficient of 0.87 was achieved. The different stages of inbreeding were analysed using restriction fragment polymorphism, microsatellite variability and amplified fragment length polymorphism. Model-based clustering of the amplified fragment length polymorphism genotypes showed that the allele frequencies of the benzimidazole-resistant strain were stable during the last eight generations. In the sensitive strain a gradual shift of allele frequencies was observed, which led to a temporary increase of the genetic diversity around the eight generations. 相似文献
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Willem J van der Laarse Ariane L des Tombe Brechje J van Beek-Harmsen Marleen B E Lee-de Groot Richard T Jaspers 《Journal of applied physiology》2005,99(6):2173-2180
The value of the diffusion coefficient for oxygen in muscle is uncertain. The diffusion coefficient is important because it is a determinant of the extracellular oxygen tension at which the core of muscle fibers becomes anoxic (Po(2crit)). Anoxic cores in muscle fibers impair muscular function and may limit adaptation of muscle cells to increased load and/or activity. We used Hill's diffusion equations to determine Krogh's diffusion coefficient (Dalpha) for oxygen in single skeletal muscle fibers from Xenopus laevis at 20 degrees C (n = 6) and in myocardial trabeculae from the rat at 37 degrees C (n = 9). The trabeculae were dissected from the right ventricular myocardium of control (n = 4) and monocrotaline-treated, pulmonary hypertensive rats (n = 5). The cross-sectional area of the preparations, the maximum rate of oxygen consumption (Vo(2 max)), and Po(2crit) were determined. Dalpha increased in the following order: Xenopus muscle fibers Dalpha = 1.23 nM.mm(2).mmHg(-1).s(-1) (SD 0.12), control rat trabeculae Dalpha = 2.29 nM.mm(2).mmHg(-1).s(-1) (SD 0.24) (P = 0.0012 vs. Xenopus), and hypertrophied rat trabeculae Dalpha = 6.0 nM.mm(2).mmHg(-1).s(-1) (SD 2.8) (P = 0.039 vs. control rat trabeculae). Dalpha increased with extracellular space in the preparation (Spearman's rank correlation coefficient = 0.92, P < 0.001). The values for Dalpha indicate that Xenopus muscle fibers cannot reach Vo(2 max) in vivo because Po(2crit) can be higher than arterial Po(2) and that hypertrophied rat cardiomyocytes can become hypoxic at the maximum heart rate. 相似文献
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Validation of soluble amyloid‐β precursor protein assays as diagnostic CSF biomarkers for neurodegenerative diseases
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Linda J.C. van Waalwijk van Doorn Marleen J. Koel‐Simmelink Ute Haußmann Hans Klafki Hanne Struyfs Philipp Linning Hans‐Joachim Knölker Harry Twaalfhoven H. Bea Kuiperij Sebastiaan Engelborghs Philip Scheltens Marcel M. Verbeek Eugeen Vanmechelen Jens Wiltfang Charlotte E. Teunissen 《Journal of neurochemistry》2016,137(1):112-121
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Sophia R. Cameron-Christie Constance F. Wells Marleen Simon Marja Wessels Candy Z.N. Tang Wenhua Wei Riku Takei Coranne Aarts-Tesselaar Sarah Sandaradura David O. Sillence Marie-Pierre Cordier Hermine E. Veenstra-Knol Matteo Cassina Kathrin Ludkig Eva Trevisson Melanie Bahlo David M. Markie Zandra A. Jenkins Stephen P. Robertson 《American journal of human genetics》2018,102(6):1115-1125
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Alain D. Dekker Yannick Vermeiren Gonny Beugelsdijk Mieke Schippers Lyanne Hassefras José Eleveld Sharina Grefelman Roelie Fopma Monique Bomer-Veenboer G. Danielle E. Oosterling Esther Scholten Marleen Tollenaere Gert Van Goethem Christine zu Eulenburg Antonia M. W. Coppus Peter P. De Deyn 《Tijdschrift voor gerontologie en geriatrie》2018,49(5):187-205
Behavioral and psychological symptoms of dementia (BPSD) have not been comprehensively studied in people with Down syndrome, despite their high risk on dementia. A novel evaluation scale was developed to identify the nature, frequency and severity of behavioral changes (83 behavioral items in 12 clinically defined sections). Central aim was to identify items that change in relation to the dementia status. Structured interviews were conducted with informants of people with Down syndrome without dementia (DS, N?=?149), with questionable dementia (DS?+?TD, N?=?65) and with diagnosed dementia (DS?+?AD, N?=?67). Group comparisons showed a pronounced increase in frequency and severity of items about anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and, eating/drinking behavior. The proportion of individuals presenting an increase was highest in the DS?+?AD group and lowest in the DS group. Interestingly, among DS?+?TD individuals, a substantial proportion already presented increased anxiety, sleep disturbances, apathy and depressive symptoms, suggesting that these changes may be early alarm signals of dementia. The scale may contribute to a better understanding of the changes, adapting daily care/support, and providing suitable therapies to people with Down syndrome. The scale needs to be optimized based on the results and experiences. The applicability, reliability and validity require further study. 相似文献
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Rob N. de Jong Frank J. Beurskens Sandra Verploegen Kristin Strumane Muriel D. van Kampen Marleen Voorhorst Wendy Horstman Patrick J. Engelberts Simone C. Oostindie Guanbo Wang Albert J. R. Heck Janine Schuurman Paul W. H. I. Parren 《PLoS biology》2016,14(1)
IgG antibodies can organize into ordered hexamers on cell surfaces after binding their antigen. These hexamers bind the first component of complement C1 inducing complement-dependent target cell killing. Here, we translated this natural concept into a novel technology platform (HexaBody technology) for therapeutic antibody potentiation. We identified mutations that enhanced hexamer formation and complement activation by IgG1 antibodies against a range of targets on cells from hematological and solid tumor indications. IgG1 backbones with preferred mutations E345K or E430G conveyed a strong ability to induce conditional complement-dependent cytotoxicity (CDC) of cell lines and chronic lymphocytic leukemia (CLL) patient tumor cells, while retaining regular pharmacokinetics and biopharmaceutical developability. Both mutations potently enhanced CDC- and antibody-dependent cellular cytotoxicity (ADCC) of a type II CD20 antibody that was ineffective in complement activation, while retaining its ability to induce apoptosis. The identified IgG1 Fc backbones provide a novel platform for the generation of therapeutics with enhanced effector functions that only become activated upon binding to target cell–expressed antigen. 相似文献