全文获取类型
收费全文 | 722篇 |
免费 | 185篇 |
国内免费 | 11篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 9篇 |
2021年 | 17篇 |
2020年 | 26篇 |
2019年 | 26篇 |
2018年 | 31篇 |
2017年 | 25篇 |
2016年 | 52篇 |
2015年 | 68篇 |
2014年 | 60篇 |
2013年 | 74篇 |
2012年 | 49篇 |
2011年 | 53篇 |
2010年 | 43篇 |
2009年 | 36篇 |
2008年 | 31篇 |
2007年 | 41篇 |
2006年 | 47篇 |
2005年 | 32篇 |
2004年 | 51篇 |
2003年 | 26篇 |
2002年 | 13篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 8篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1970年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有918条查询结果,搜索用时 15 毫秒
91.
Li D Pickell L Liu Y Rozen R 《Birth defects research. Part A, Clinical and molecular teratology》2006,76(1):55-59
BACKGROUND: The etiology of neural tube defects (NTDs) is multifactorial, with environmental and genetic determinants. Folate supplementation prevents the majority of NTDs, and a polymorphism in methylenetetrahydrofolate reductase (MTHFR) has become recognized as a genetic risk factor. The mechanisms by which folate affects NTD development are unclear. The Splotch (Sp) mouse is a well-characterized mouse model for studying spontaneous NTDs. To assess the potential interaction between folate metabolism and the Sp mutant in NTD development, we studied mice with both Sp and Mthfr mutations, as well as the interaction between Sp and low dietary folate. METHODS: Wild-type, single Mthfr+/-mutant, single Sp/+mutant, and double mutant (Mthfr+/-, Sp/+) female mice were mated with males of the same genotype. Embryos were examined for NTDs on gestational day (GD) 13.5. To investigate the effects of folate deficiency on Sp mice, Sp/+female mice were fed a control diet (CD), a moderately folic acid-deficient diet (MFADD), or a severely folic acid-deficient diet (SFADD). They were mated with Sp/+males and the embryos were examined. RESULTS: There were no differences in the incidence or severity of NTDs in embryos from double-mutant mating pairs compared to those from single Sp mutants. Embryos from Mthfr+/-dams did not exhibit NTDs. Diets deficient in folate did not influence the incidence or severity of NTDs in embryos from Sp/+mice. CONCLUSIONS: We did not observe an interaction between Sp and Mthfr mutations, or between the Sp mutation and low dietary folate, in NTD development in Splotch mice. 相似文献
92.
An episode of hyperthermia is not uncommon during pregnancy. The consequences depend on the extent of temperature elevation, its duration, and the stage of development when it occurs. Mild exposures during the preimplantation period and more severe exposures during embryonic and fetal development often result in prenatal death and abortion. Hyperthermia also causes a wide range of structural and functional defects. The central nervous system (CNS) is most at risk probably because it cannot compensate for the loss of prospective neurons by additional divisions by the surviving neuroblasts and it remains at risk at stages throughout pre- and postnatal life. In experimental animals the most common defects are of the neural tube, microphthalmia, cataract, and micrencephaly, with associated functional and behavioral problems. Defects of craniofacial development including clefts, the axial and appendicular skeleton, the body wall, teeth, and heart are also commonly found. Nearly all these defects have been found in human epidemiological studies following maternal fever or hyperthermia during pregnancy. Suggested future human studies include problems of CNS function after exposure to influenza and fever, including mental retardation, schizophrenia, autism, and cerebral palsy. 相似文献
93.
Congenital heart defects are known to be associated with facial dysmorphism and other congenital anomalies. Oculo-facio-cardio-dental (OFCD) syndrome is one such rare multiple congenital anomaly syndrome inherited as an X-linked dominant condition characterized by congenital cataracts, multiple minor facial dysmorphic features, congenital heart defects and dental anomalies. It is unrecognized by many medical and dental professionals. Only 21 cases have been reported so far. This syndrome is often misrecognized as rubella embryopathy because of association of congenital cataract with cardiac anomalies. It is usually the orthodontists who diagnose the syndrome based on typical findings on dental panoramic radiographs. But we suspected our patient to be having OFCD syndrome based on typical facial dysmorphism, ocular and cardiac defects, and finally it was confirmed after noticing typical dental radiographic findings. 相似文献
94.
Zai Chang Qiuting Feng Teng Teng Congjia Shan Brian A. Hemmings Zhongzhou Yang 《Developmental biology》2010,347(2):384-391
The PI3K-PDK1-PKB/Akt (PI3K, phosphoinositide-3 kinase; PDK1, phosphoinositide-dependent protein kinase 1; PKB, protein kinase B) signaling pathway plays a critical role in a variety of biological processes including cell survival, growth and proliferation, metabolism and organogenesis. Previously, we generated Akt1-deficient mice and found high neonatal mortality with unknown causes. Here we report that histological analysis of Akt1-deficient embryos and newborns revealed heart defects and decreased cell proliferation. Echocardiographic study of Akt1-deficient mice indicated decreased heart function. Further investigation revealed that Akt1 deficiency caused substantial activation of p38MAPK in the heart. Breeding the Akt1-deficient mice to mice that were heterozygous for a null p38α partially rescued the heart defects, significantly decreased post-natal mortality, and restored normal patterns of cardiomyocyte proliferation. Our study suggests that Akt1 is essential for heart development and function, in part, through suppression of p38MAPK activation. 相似文献
95.
E. Ahmed Ahmed I. Abo-Ahmed Fatgzim Latifi 《Saudi Journal of Biological Sciences》2021,28(9):5325-5331
The nasal septal island (NSI) is a sensory patch of neuroepithelium located within the soft tissue of the nasal septum in dromedaries. The island has unique anatomical features, including the specialized subepithelial glands. The aim of the present study was to describe the microscopic features and ultrastructure of these subepithelial glands and to speculate the possible functions. A total of 10 camel heads were used for the study. Unlike the serous and mucous airway glands, the NSI glands’ ultrastructural features were typical for cells of the (Amine Precursor Uptake and Decarboxylation, APUD) system. These features were included, membrane bound secretory vesicles of varying electron density, smooth endoplasmic reticulum in the form of vesicles; electron dense mitochondria, abundant rough endoplasmic reticulum and free ribosomes. Alcian-PAS identifiable mucus granules were not observed, except for few clusters of cells, located at the luminal surface. The probable functions were discussed on basis of cellular morphology and context. In a conclusion, the NSI subepithelial glands in dromedaries had unique anatomical structures, and as many other APUD cells, they had the machinery required for synthesis of a variable number of biologically active peptides, amines and chemical mediators. 相似文献
96.
CYP4B1 is highly expressed in rat nasal respiratory mucosa, and to a lesser extent in olfactory mucosa. Examination of high-power photomicrographs suggests that CYP4B1 may be a secreted protein, based on the fact that immunoreactivity appears to be present in the lumens of ducts of Bowman's glands (rather than intracellular localization, as we observed with an antibody recognizing CYP2F4) and in secretory granules in respiratory mucosa. Furthermore, anti-CYP4B1 immunoreactivity is present on the surface of both respiratory and olfactory mucosa. We used SignalP 3.0 analysis to ascertain the likelihood that rat CYP4B1 is a secreted protein. While this analysis does not suggest that rat CYP4B1 is a secreted protein, several other cytochrome P450 enzymes were predicted to be secreted proteins. The observation that multiple human cytochrome P450s appear to be secreted proteins helps to explain the appearance of anti-cytochrome P450 antigens in cases of human autoimmune liver diseases. 相似文献
97.
13q deletion syndrome is a rare genetic disorder caused by deletions of the long arm of chromosome 13. Patients with 13q deletion display a variety of phenotypic features. We describe a one-year-old female patient with congenital heart defects (CHD), facial anomalies, development and mental retardation. We identified a 12.75Mb deletion in chromosome region 13q33.1-34 with high resolution SNP Array (Human660W-Quad, Illumina, USA). This chromosome region contains about 55 genes, including EFNB2, ERCC5, VGCNL1, F7, and F10. Comparing our findings with previously reported 13q deletion patients with congenital heart defects, we propose that the 13q33.1-34 deletion region might contain key gene(s) associated with cardiac development. Our study also identified a subclinical deficiency of Factors VII and X in our patient with Group 3 of 13q deletion syndrome. 相似文献
98.
Guatelli-Steinberg D Ferrell RJ Spence J 《American journal of physical anthropology》2012,148(2):191-204
Physiological stress, such as malnutrition or illness, can disrupt normal enamel growth, resulting in linear enamel hypoplasias (LEHs). Although ecological factors may contribute to LEH expression, other factors, such as surface abrasion and enamel growth variables, are also likely to be involved. Attention to these other factors is necessary before we can begin to understand what LEH might signify in terms of ecological sources of physiological stress in non-human primates. This study focuses on assessing the contribution of these other factors to variation in LEH expression within and across great ape taxa. Here, we present LEH data from unabraded crown regions in samples of seven great ape species. We analyze these data with respect to lateral enamel formation time and the angles that striae of Retzius make with the enamel surface, as these variables are expected to affect variation in LEH expression. We find that although the duration of enamel formation is associated with sex differences in LEH expression, it is not clearly related to taxonomic variation in LEH expression, and does not explain the low frequency of LEH in mountain gorillas found in this and a previous study. Our data on striae of Retzius angles suggest that these influence LEH expression along the tooth crown and may contribute to the consistently high frequencies of LEH seen in Pongo in this and previous studies. We suggest that future work aimed at understanding species variation in these angles is crucial to evaluating taxonomic patterns of LEH expression in great apes. 相似文献
99.
CD4 T cells, and especially T follicular helper cells, are critical for the generation of a robust humoral response to an infection or vaccination. Importantly, immunosenescence affects CD4 T‐cell function, and the accumulation of intrinsic defects decreases the cognate helper functions of these cells. However, much less is known about the contribution of the aged microenvironment to this impaired CD4 T‐cell response. In this study, we have employed a preclinical model to determine whether the aged environment contributes to the defects in CD4 T‐cell functions with aging. Using an adoptive transfer model in mice, we demonstrate for the first time that the aged microenvironment negatively impacts at least three steps of the CD4 T‐cell response to antigenic stimulation. First, the recruitment of CD4 T cells to the spleen is reduced in aged compared to young hosts, which correlates with dysregulated chemokine expression in the aged organ. Second, the priming of CD4 T cells by DCs is reduced in aged compared to young mice. Finally, naïve CD4 T cells show a reduced transition to a T follicular helper cell phenotype in the aged environment, which impairs the subsequent generation of germinal centers. These studies have provided new insights into how aging impacts the immune system and how these changes influence the development of immunity to infections or vaccinations. 相似文献
100.
Li H Gao F Ma L Jiang J Miao J Jiang M Fan Y Wang L Wu D Liu B Wang W Lui VC Yuan Z 《Journal of cellular and molecular medicine》2012,16(7):1606-1617
Neural tube defects (NTDs) are complex congenital malformations resulting from incomplete neurulation in embryo. Despite surgical repair of the defect, most of the patients who survive with NTDs have a multiple system handicap due to neuron deficiency of the defective spinal cord. In this study, we successfully devised a prenatal surgical approach and transplanted mesenchymal stem cells (MSCs) to foetal rat spinal column to treat retinoic acid induced NTDs in rat. Transplanted MSCs survived, grew and expressed markers of neurons, glia and myoblasts in the defective spinal cord. MSCs expressed and perhaps induced the surrounding spinal tissue to express neurotrophic factors. In addition, MSC reduced spinal tissue apoptosis in NTD. Our results suggested that prenatal MSC transplantation could treat spinal neuron deficiency in NTDs by the regeneration of neurons and reduced spinal neuron death in the defective spinal cord. 相似文献