全文获取类型
收费全文 | 165篇 |
免费 | 16篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2017年 | 2篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 9篇 |
2012年 | 10篇 |
2011年 | 2篇 |
2010年 | 6篇 |
2009年 | 6篇 |
2008年 | 6篇 |
2007年 | 6篇 |
2006年 | 4篇 |
2005年 | 1篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 8篇 |
1986年 | 3篇 |
1985年 | 11篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 7篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
排序方式: 共有181条查询结果,搜索用时 31 毫秒
71.
Kornelia Neveling Lilian A. Martinez-Carrera Irmgard Hölker Angelien Heister Aad Verrips Seyyed Mohsen Hosseini-Barkooie Christian Gilissen Sascha Vermeer Maartje Pennings Rowdy Meijer Margot te Riele Catharina J.M. Frijns Oksana Suchowersky Linda MacLaren Sabine Rudnik-Schöneborn Richard J. Sinke Klaus Zerres R. Brian Lowry Henny H. Lemmink Lutz Garbes Joris A. Veltman Helenius J. Schelhaas Hans Scheffer Brunhilde Wirth 《American journal of human genetics》2013
72.
Federica Boraldi Maria Garcia-Fernandez Chiara Paolinelli-deVincenzi Giulia Annovi Leon Schurgers Cees Vermeer Paolo Cianciulli Ivonne Ronchetti Daniela Quaglino 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):2077-2084
A number of beta-thalassemia (β-thal) patients in the course of the disease exhibit ectopic calcification affecting skin, eyes and the cardiovascular system. Clinical and histopathological features have been described similar to those in pseudoxanthoma elasticum (PXE), although different genes are affected in the two diseases. Cultured dermal fibroblasts from β-thal patients with and without PXE-like clinical manifestations have been compared for parameters of redox balance and for the expression of proteins, which have been already associated with the pathologic mineralisation of soft connective tissues. Even though oxidative stress is a well-known condition of β-thal patients, our results indicate that the occurrence of mineralized elastin is associated with a more pronounced redox disequilibrium, as demonstrated by the intracellular increase of anion superoxide and of oxidized proteins and lipids. Moreover, fibroblasts from β-thal PXE-like patients are characterized by decreased availability of carboxylated matrix Gla protein (MGP), as well as by altered expression of proteins involved in the vitamin K-dependent carboxylation process. Results demonstrate that elastic fibre calcification is promoted when redox balance threshold levels are exceeded and the vitamin K-dependent carboxylation process is affected decreasing the activity of MGP, a well-known inhibitor of ectopic calcification. Furthermore, independently from the primary gene defect, these pathways are similarly involved in fibroblasts from PXE and from β-thal PXE-like patients as well as in other diseases leading to ectopic calcification, thus suggesting that can be used as markers of pathologic mineralisation. 相似文献
73.
Jan Vermeer Julio C. Tello-Alvarado Sergio Moreno-Moreno Fernando Guerra-Vásquez 《International journal of primatology》2011,32(4):924-930
White-browed titi monkeys (Callicebus discolor) have one of the largest distribution ranges of all titi monkey species, occurring from central Peru to southern Colombia.
During a long-term study on the distribution of titi monkeys and other primates in Peru, we conducted extensive surveys in
the San Martin Department of northeastern Peru. We encountered Callicebus discolor at the left bank of the Huallaga River, where the species most probably lives in sympatry with endemic San Martin titi monkeys
(Callicebus oenanthe). Our study reveals an important extension of its formerly known distribution range. Massive deforestation activities in
the region make studies on the habitat preferences of both species difficult, as most titi monkeys are confined to the remaining
small remnants of the original forest. Urgent conservation measures are necessary to preserve the last lowland forests of
San Martin. 相似文献
74.
Vermeer PD Bell M Lee K Vermeer DW Wieking BG Bilal E Bhanot G Drapkin RI Ganesan S Klingelhutz AJ Hendriks WJ Lee JH 《PloS one》2012,7(1):e30447
In non-cancerous cells, phosphorylated proteins exist transiently, becoming de-phosphorylated by specific phosphatases that terminate propagation of signaling pathways. In cancers, compromised phosphatase activity and/or expression occur and contribute to tumor phenotype. The non-receptor phosphatase, PTPN13, has recently been dubbed a putative tumor suppressor. It decreased expression in breast cancer correlates with decreased overall survival. Here we show that PTPN13 regulates a new signaling complex in breast cancer consisting of ErbB2, Src, and EphrinB1. To our knowledge, this signaling complex has not been previously described. Co-immunoprecipitation and localization studies demonstrate that EphrinB1, a PTPN13 substrate, interacts with ErbB2. In addition, the oncogenic V660E ErbB2 mutation enhances this interaction, while Src kinase mediates EphrinB1 phosphorylation and subsequent MAP Kinase signaling. Decreased PTPN13 function further enhances signaling. The association of oncogene kinases (ErbB2, Src), a signaling transmembrane ligand (EphrinB1) and a phosphatase tumor suppressor (PTPN13) suggest that EphrinB1 may be a relevant therapeutic target in breast cancers harboring ErbB2-activating mutations and decreased PTPN13 expression. 相似文献
75.
76.
Marloes Vermeer Hillechiena H Kuper Hein J Bernelot Moens Monique Hoekstra Marcel D Posthumus Piet LCM van Riel Mart AFJ van de Laar 《Arthritis research & therapy》2012,14(6):R254
Introduction
Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments.Methods
A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations.Results
The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28.Conclusions
The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice. 相似文献77.
Ian M Copple Amy E Mercer James Firman Gail Donegan Bram Herpers Michael HL Wong James Chadwick Andreia D Bringela Maria LS Cristiano Bob van de Water Stephen A Ward Paul M O’Neill B Kevin Park 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1045-1055
Semisynthetic artemisinin-based therapies are the first-line treatment for P. falciparum malaria, but next-generation synthetic drug candidates are urgently required to improve availability and respond to the emergence of artemisinin-resistant parasites. Artemisinins are embryotoxic in animal models and induce apoptosis in sensitive mammalian cells. Understanding the cytotoxic propensities of antimalarial drug candidates is crucial to their successful development and utilization. Here, we demonstrate that, similarly to the model artemisinin artesunate (ARS), a synthetic tetraoxane drug candidate (RKA182) and a trioxolane equivalent (FBEG100) induce embryotoxicity and depletion of primitive erythroblasts in a rodent model. We also show that RKA182, FBEG100 and ARS are cytotoxic toward a panel of established and primary human cell lines, with caspase-dependent apoptosis and caspase-independent necrosis underlying the induction of cell death. Although the toxic effects of RKA182 and FBEG100 proceed more rapidly and are relatively less cell-selective than that of ARS, all three compounds are shown to be dependent upon heme, iron and oxidative stress for their ability to induce cell death. However, in contrast to previously studied artemisinins, the toxicity of RKA182 and FBEG100 is shown to be independent of general chemical decomposition. Although tetraoxanes and trioxolanes have shown promise as next-generation antimalarials, the data described here indicate that adverse effects associated with artemisinins, including embryotoxicity, cannot be ruled out with these novel compounds, and a full understanding of their toxicological actions will be central to the continuing design and development of safe and effective drug candidates which could prove important in the fight against malaria. 相似文献
78.
The combined determination of indolyl-3-acetic and abscissic acid in plant materials 总被引:1,自引:0,他引:1
A method for isoelectric focusing of antibodies in agarose gels with ampholytes synthesized in the laboratory from pentaethylenehexamine is presented. The ampholytes are easy to prepare, give results comparable to those with commercial ampholytes, and are much less expensive. Substituting agrarose bonded to plastic film for the polyacrylamide gels on glass plates commonly used offers many advantages and enhances the usefulness of isoelectric focusing as a tool for studying antibody molecules. 相似文献
79.
80.
Photosynthetic parameters of birch (Betula pendula Roth) leaves growing in normal and in CO2 - and O3 - enriched atmospheres 总被引:2,自引:2,他引:0
H. EICHELMANN V. OJA B. RASULOV E. PADU I. BICHELE H. PETTAI T. MÖLS I. KASPAROVA E. VAPAAVUORI & A. LAISK 《Plant, cell & environment》2004,27(4):479-495
Two silver birch (Betula pendula Roth) clones K1659 and V5952 were grown in open‐top chambers over 3 years (age 7–9 years). The treatments were increased CO2 concentration (+CO2, 72 Pa), increased O3 concentration (+O3, 2 × ambient O3 with seasonal AOT40 up to 28 p.p.m. h) and in combination (+CO2 + O3). Thirty‐seven photosynthetic parameters were measured in the laboratory immediately after excising leaves using a computer‐operated routine of gas exchange and optical measurements. In control leaves the photosynthetic parameters were close to the values widely used in a model (Farquhar, von Caemmerer and Berry, Planta 149, 78–90, 1980). The distribution of chlorophyll between photosystem II and photosystem I, intrinsic quantum yield of electron transport, uncoupled turnover rate of Cyt b6f, Rubisco specificity and Km (CO2) were not influenced by treatments. Net photosynthetic rate responded to +CO2 with a mean increase of 17% in both clones. Dry weight of leaves increased, whereas protein, especially Rubisco content and the related photosynthetic parameters decreased. Averaged over 3 years, eight and 17 mechanistically independent parameters were significantly influenced by the elevated CO2 in clones K1659 and V5952, respectively. The elevated O3 caused a significant decrease in the average photosynthetic rate of clone V5952, but not of clone K1659. The treatment caused changes in one parameter of clone K1659 and in 11 parameters of clone V5952. Results of the combined treatment indicated that +O3 had less effect in the presence of +CO2 than alone. Interestingly, changes in the same photosynthetic parameters were observed in chamberless grown trees of clone V5952 as under +O3 treatment in chambers, but this was not observed for clone K1659. These results suggest that during chronic fumigation, at concentrations below the threshold of visible leaf injuries, ozone influenced the photosynthetic parameters as a general stress factor, in a similar manner to weather conditions that were more stressful outside the chambers. According to this hypothesis, the sensitivity of a species or a clone to ozone is expected to depend on the growth conditions: the plant is less sensitive to ozone if the conditions are close to optimal and it is more sensitive to ozone under conditions of stress. 相似文献