全文获取类型
收费全文 | 832篇 |
免费 | 53篇 |
出版年
2023年 | 5篇 |
2022年 | 7篇 |
2021年 | 10篇 |
2020年 | 7篇 |
2019年 | 10篇 |
2018年 | 8篇 |
2017年 | 10篇 |
2016年 | 25篇 |
2015年 | 32篇 |
2014年 | 33篇 |
2013年 | 38篇 |
2012年 | 53篇 |
2011年 | 41篇 |
2010年 | 23篇 |
2009年 | 28篇 |
2008年 | 33篇 |
2007年 | 26篇 |
2006年 | 28篇 |
2005年 | 28篇 |
2004年 | 35篇 |
2003年 | 43篇 |
2002年 | 36篇 |
2001年 | 29篇 |
2000年 | 21篇 |
1999年 | 23篇 |
1998年 | 13篇 |
1997年 | 9篇 |
1996年 | 10篇 |
1995年 | 4篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 14篇 |
1991年 | 9篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 14篇 |
1987年 | 16篇 |
1986年 | 9篇 |
1985年 | 11篇 |
1984年 | 14篇 |
1983年 | 6篇 |
1981年 | 9篇 |
1979年 | 9篇 |
1977年 | 10篇 |
1976年 | 9篇 |
1975年 | 9篇 |
1972年 | 5篇 |
1971年 | 5篇 |
1966年 | 4篇 |
1965年 | 5篇 |
排序方式: 共有885条查询结果,搜索用时 15 毫秒
101.
Merja Hurskainen Florence Ruggiero Pasi H?gg Taina Pihlajaniemi Pirkko Huhtala 《The Journal of biological chemistry》2010,285(8):5258-5265
The C-terminal end of collagen XV, restin, has been the focus of several studies, but the functions of full-length collagen XV have remained unknown. We describe here studies on the production, purification, and function of collagen XV and the production of a monoclonal N-terminal antibody to it. Full-length human collagen XV was produced in insect cells using baculoviruses and purified from the cell culture medium. The yield was 15 mg/liter of cell culture medium. The collagen XV was shown to be trimeric, with disulfide bonds in the collagenous region. Rotary shadowing electron microscopy revealed rod-like molecules with a mean length of 241.8 nm and with a globular domain at one end. The globular domain was verified to be the N-terminal end by N-terminal antibody binding. The molecules show flexibility in their conformation, presumably due to the many interruptions in their collagenous domains. The ability of collagen XV to serve as a substrate for cells was tested in cell adhesion assays, and it was shown that cells did not bind to collagen XV-coated surfaces. When added to the culture medium of fibroblasts and fibrosarcoma cells, however, collagen XV rapidly bound to their fibronectin network. Solid phase assays showed that collagen XV binds to fibronectin, laminin, and vitronectin and that it binds to the collagen/gelatin-binding domain of fibronectin. No binding was detected to fibrillar collagens, fibril-associated collagens, or decorin. Interestingly, collagen XV was found to inhibit the adhesion and migration of fibrosarcoma cells when present in fibronectin-containing matrices. 相似文献
102.
Witt CC Burkart C Labeit D McNabb M Wu Y Granzier H Labeit S 《The EMBO journal》2006,25(16):3843-3855
The precise assembly of the highly organized filament systems found in muscle is critically important for its function. It has been hypothesized that nebulin, a giant filamentous protein extending along the entire length of the thin filament, provides a blueprint for muscle thin filament assembly. To test this hypothesis, we generated a KO mouse model to investigate nebulin functions in vivo. Nebulin KO mice assemble thin filaments of reduced lengths and approximately 15% of their Z-disks are abnormally wide. Our data demonstrate that nebulin functions in vivo as a molecular ruler by specifying pointed- and barbed-end thin filament capping. Consistent with the shorter thin filament length of nebulin deficient mice, maximal active tension was significantly reduced in KO animals. Phenotypically, the murine model recapitulates human nemaline myopathy (NM), that is, the formation of nemaline rods combined with severe skeletal muscle weakness. The myopathic changes in the nebulin KO model include depressed contractility, loss of myopalladin from the Z-disk, and dysregulation of genes involved in calcium homeostasis and glycogen metabolism; features potentially relevant for understanding human NM. 相似文献
103.
104.
Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Huebner A Mann P Rohde E Kaindl AM Witt M Verkade P Jakubiczka S Menschikowski M Stoltenburg-Didinger G Koehler K 《Molecular and cellular biology》2006,26(5):1879-1887
Triple A syndrome is a human autosomal recessive disorder characterized by adrenal insufficiency, achalasia, alacrima, and neurological abnormalities affecting the central, peripheral, and autonomic nervous systems. In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes. To analyze the function of the gene in the context of the whole organism and in an attempt to obtain an animal model for human triple A syndrome, we generated mice lacking a functional Aaas gene. The Aaas-/- animals were found to be externally indistinguishable from their wild-type littermates, although their body weight was on the average lower than that of wild-type mice. Histological analysis of various tissues failed to reveal any differences between Aaas-/- and wild-type mice. Aaas-/- mice exhibit unexpectedly mild abnormal behavior and only minor neurological deficits. Our data show that the lack of ALADIN in mice does not lead to a triple A syndrome-like disease. Thus, in mice either the function of ALADIN differs from that in humans, its loss can be readily compensated for, or additional factors, such as environmental conditions or genetic modifiers, contribute to the disease. 相似文献
105.
Williams RE Aberg L Autti T Goebel HH Kohlschütter A Lönnqvist T 《Biochimica et biophysica acta》2006,1762(10):865-872
For the majority of families affected by one of the neuronal ceroid lipofuscinoses (NCLs), a biochemical and/or genetic diagnosis can be achieved. In an individual case this information not only increases understanding of the condition but also may influence treatment choices and options. The presenting clinical features prompt initial investigation and also guide clinical care. The clinical labels "infantile NCL", "late infantile NCL" and "juvenile NCL", therefore remain useful in practice. In unusual or atypical cases ultra-structural analysis of white blood cells or other tissue samples enables planning and prioritisation of biochemical and genetic tests.This review describes current methods available to achieve clinical, pathological, biochemical and genetic diagnosis in children presenting with symptoms suggestive of one of the NCLs. 相似文献
106.
Generation of cloned transgenic pigs rich in omega-3 fatty acids 总被引:33,自引:0,他引:33
Lai L Kang JX Li R Wang J Witt WT Yong HY Hao Y Wax DM Murphy CN Rieke A Samuel M Linville ML Korte SW Evans RW Starzl TE Prather RS Dai Y 《Nature biotechnology》2006,24(4):435-436
Meat products are generally low in omega-3 (n-3) fatty acids, which are beneficial to human health. We describe the generation of cloned pigs that express a humanized Caenorhabditis elegans gene, fat-1, encoding an n-3 fatty acid desaturase. The hfat-1 transgenic pigs produce high levels of n-3 fatty acids from n-6 analogs, and their tissues have a significantly reduced ratio of n-6/n-3 fatty acids (P < 0.001). 相似文献
107.
108.
109.
Liu D Wood NB Witt N Hughes AD Thom SA Xu XY 《Journal of biomechanical engineering》2012,134(1):014501
The retinal arterial network structure can be altered by systemic diseases such as hypertension and diabetes. In order to compare the energy requirement for maintaining retinal blood flow and vessel wall metabolism between normal and hypertensive subjects, 3D hypothetical models of a representative retinal arterial bifurcation were constructed based on topological features derived from retinal images. Computational analysis of blood flow was performed, which accounted for the non-Newtonian rheological properties of blood and peripheral vessel resistance. The results suggested that the rate of energy required to maintain the blood flow and wall metabolism is much lower for normal subjects than for hypertensives, with the latter requiring 49.2% more energy for an entire retinal arteriolar tree. Among the several morphological factors, length-to-diameter ratio was found to have the most significant influence on the overall energy requirement. 相似文献
110.
Quiel A Jürgen B Greinacher A Lassen S Wörl R Witt S Schweder T 《Biosensors & bioelectronics》2012,36(1):207-211
To prevent and treat immune-mediated platelet disorders (e.g. neonatal allo-immune thrombocytopenia and platelet transfusion refractoriness) the causative idiotypic platelet-reactive antibodies have to be detected with high sensitivity and specificity. The "Monoclonal Antibody Immobilization Platelet Assay" (MAIPA) is the diagnostic gold standard for immunotyping sera with respect to alloantibodies against human platelet antigens (HPA). However, it is labor-intensive and time-consuming. In this work, an automated protein chip assay (enzyme-linked sandwich immunoassay) based on interdigitated gold microelectrodes in combination with an electrical read-out system was developed and optimized. For this purpose, specific capture antibodies were immobilized on the gold electrodes. The binding of the target is detected via an enzyme-labeled detection antibody by a redox-recycling process that corresponds to the amount of bound target molecule. With this electrical chip assay it is possible to detect antibodies against HPA-1a, HPA-5b and HLA with high sensitivity and specificity in less than half the duration of the MAIPA protocol with similar intra- and interassay variance. 相似文献