全文获取类型
收费全文 | 226篇 |
免费 | 14篇 |
专业分类
240篇 |
出版年
2021年 | 3篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 8篇 |
2013年 | 16篇 |
2012年 | 19篇 |
2011年 | 9篇 |
2010年 | 20篇 |
2009年 | 6篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 4篇 |
2005年 | 10篇 |
2004年 | 7篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 2篇 |
1994年 | 7篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1968年 | 1篇 |
1954年 | 1篇 |
1953年 | 1篇 |
1927年 | 1篇 |
排序方式: 共有240条查询结果,搜索用时 15 毫秒
71.
Elizabeth Lonsdorf Dominic Travis Richard Ssuna Emma Lantz Michael Wilson Kathryn Gamble Karen Terio Fabian Leendertz Bernhard Ehlers Brandon Keele Beatrice Hahn Thomas Gillespie Joel Pond Jane Raphael Anthony Collins 《Primates; journal of primatology》2014,55(1):89-99
Infectious diseases are widely presumed to be one of the greatest threats to ape conservation in the wild. Human diseases are of particular concern, and the costs and benefits of human presence in protected areas with apes are regularly debated. While numerous syndromes with fatal outcomes have recently been described, precise identification of pathogens remains difficult. These diagnostic difficulties are compounded by the fact that direct veterinary intervention on wild apes is quite rare. Here we present the unique case of a wild chimpanzee at Gombe National Park that was observed with a severe illness and was subsequently examined and treated in the field. Multiple specimens were collected and tested with the aim of identifying the pathogen responsible for the illness. Our findings represent the first extensive screening of a living wild chimpanzee, yet despite our efforts, the cause and source of illness remain unknown. Nevertheless, our findings represent valuable baseline data for the ape conservation community and for comparison with other recent findings. In addition, we present the case here to demonstrate the planning required and multiple types of expertise necessary to maximize the amount of data obtained from such a rare intervention, and to provide lessons learned for future studies. 相似文献
72.
Short tertatolol treatment does not impair the hormone and metabolic responses to exercise and hypoglycemia in diabetics 总被引:1,自引:0,他引:1
Beta-blockers can precipitate hypoglycemia and mask its warning signs. Ten male insulin-dependent, otherwise healthy diabetic patients underwent two submaximal exercise tests and two insulin-induced hypoglycemic events (0.2 u/Kg short-acting insulin IV) after six days administration of placebo followed by tertatolol, a non selective beta-blocker (5 mg once daily). Tertatolol modified neither the exercise-induced changes in blood glucose, lactate and plasma unesterified fatty acid levels, nor those of counter regulatory hormones (glucagon, growth hormone, cortisol), while blood pressure, heart rate and plasma renin activity were significantly reduced, proving that tertatolol had actually been ingested, and was active. During the insulin-induced hypoglycemia, similarly tertatolol did not modify the course of the plasma fuels and hormones. Particularly, hypoglycemia was neither deeper nor more prolonged in the presence than in the absence of tertatolol. Warning symptoms were not affected except for palpitations which were not perceived. These results suggest that tertatolol did not precipitate hypoglycemia following exercise, and did not aggravate insulin-induced hypoglycemia in short term administration, and in otherwise healthy diabetic patients. 相似文献
73.
Jan Bergstr?m Kerstin Cederlund Barbro Dahlén Ann-Sofie Lantz Maria Skedinger Lena Palmberg Britt-Marie Sundblad Kjell Larsson 《PloS one》2013,8(3)
The association between chronic obstructive pulmonary disease (COPD) and periodontal disease is sparsely studied. The aim was to describe the co-variation of periodontitis and lung function impairment in smokers. The hypothesis was that the destructive processes in the mouth and the lungs are interdependent due to a general individual susceptibility to detrimental effects of tobacco smoke. Smokers with COPD (n = 28) stage II and III according to GOLD guidelines and smokers without COPD (n = 29) and healthy non-smokers (n = 23) participated in the study. The groups of smokers were matched for cumulative exposure to tobacco smoke. Radiographic, general and dental clinical examination, lung function measurements and quality of life (SF-36) assessment were conducted. The relationship between respiratory and dental outcomes was analyzed. Dental health, assessed by plaque, gingival bleeding, periodontal pocket depth and loss of teeth was impaired in the smokers compared with non-smokers with no major differences between smokers with and without COPD. There was, however, a weak correlation between periodontitis and emphysema/impaired diffusion capacity. Impaired quality of life was associated with smoking and impaired lung function but not influenced by dental status. In conclusion periodontitis was strongly associated with smoking, weakly associated with lung tissue destruction and very weakly or even not at all associated with chronic airflow limitation. The results indicate that, although there was a co-variation between periodontitis and pathologic lung processes in smokers, the risk of developing COPD, as defined by spirometric outcomes, is not associated with the risk of impaired dental health in smokers. 相似文献
74.
75.
76.
Simon Carlsen Parayil Kumaran Ajikumar Luca Riccardo Formenti Kang Zhou Too Heng Phon Michael Lynge Nielsen Anna Eliasson Lantz Morten C. Kielland-Brandt Gregory Stephanopoulos 《Applied microbiology and biotechnology》2013,97(13):5753-5769
Transfer of a biosynthetic pathway between evolutionary distant organisms can create a metabolic shunt capable of bypassing the native regulation of the host organism, hereby improving the production of secondary metabolite precursor molecules for important natural products. Here, we report the engineering of Escherichia coli genes encoding the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway into the genome of Saccharomyces cerevisiae and the characterization of intermediate metabolites synthesized by the MEP pathway in yeast. Our UPLC-MS analysis of the MEP pathway metabolites from engineered yeast showed that the pathway is active until the synthesis of 2-C-methyl-d-erythritol-2,4-cyclodiphosphate, but appears to lack functionality of the last two steps of the MEP pathway, catalyzed by the [4Fe–4S] iron sulfur cluster proteins encoded by ispG and ispH. In order to functionalize the last two steps of the MEP pathway, we co-expressed the genes for the E. coli iron sulfur cluster (ISC) assembly machinery. By deleting ERG13, thereby incapacitating the mevalonate pathway, in conjunction with labeling experiments with U–13C6 glucose and growth experiments, we found that the ISC assembly machinery was unable to functionalize ispG and ispH. However, we have found that leuC and leuD, encoding the heterodimeric iron–sulfur cluster protein, isopropylmalate isomerase, can complement the S. cerevisiae leu1 auxotrophy. To our knowledge, this is the first time a bacterial iron–sulfur cluster protein has been functionally expressed in the cytosol of S. cerevisiae under aerobic conditions and shows that S. cerevisiae has the capability to functionally express at least some bacterial iron–sulfur cluster proteins in its cytosol. 相似文献
77.
Priscilla TY Law Siaw Shi Boon Chenghua Hu Raymond WM Lung Grace PY Cheung Wendy CS Ho Zigui Chen Paola Massimi Miranda Thomas David Pim Lawrence Banks Paul KS Chan 《Journal of cellular and molecular medicine》2019,23(2):1517-1527
Human papillomavirus 58 (HPV58) ranks the second or third in East Asian cervical cancers. Current studies on HPV58 are scarce and focus on the prototype. Previously, we identified the three most common circulating HPV58 E7 strains contained amino acid alterations: G41R/G63D (51%), T20I/G63S (22%) and T74A/D76E (14%) respectively. Among them, the T20I/G63S variant (V1) had a stronger epidemiological association with cervical cancer. We therefore suggested that V1 possessed stronger oncogenicity than the other two variants. Here, we performed phenotypic assays to characterize and compare their oncogenicities with HPV58 E7 prototype. Our results showed that overexpression of V1 conferred a higher colony‐forming ability to primary murine epithelial cells than prototype (P < 0.05) and other variants, implicating its higher immortalising potential. Further experiments showed that both V1 and prototype enhanced the anchorage‐independent growth of NIH/3T3 cells (P < 0.001), implicating their stronger transforming power than the two other variants. Moreover, they possessed an increased ability to degrade pRb (P < 0.001), which is a major effector pathway of E7‐driven oncogenesis. Our work represents the first study to compare the oncogenicities of HPV58 E7 prototype and variants. These findings deepened our understanding of HPV58 and might inform clinical screening and follow‐up strategy. 相似文献
78.
79.
Sherin Antony Peeyush Kumar T Jobin Mathew TR Anju CS Paulose 《Journal of biomedical science》2010,17(1):7
Glucose homeostasis in humans is an important factor for the functioning of nervous system. Hypoglycemia and hyperglycemia is found to be associated with central and peripheral nerve system dysfunction. Changes in acetylcholine receptors have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS). In the present study we showed the effects of insulin induced hypoglycemia and streptozotocin induced diabetes on the cerebellar cholinergic receptors, GLUT3 and muscle cholinergic activity. Results showed enhanced binding parameters and gene expression of Muscarinic M1, M3 receptor subtypes in cerebellum of diabetic (D) and hypoglycemic group (D + IIH and C + IIH). α7nAchR gene expression showed a significant upregulation in diabetic group and showed further upregulated expression in both D + IIH and C + IIH group. AchE expression significantly upregulated in hypoglycemic and diabetic group. ChAT showed downregulation and GLUT3 expression showed a significant upregulation in D + IIH and C + IIH and diabetic group. AchE activity enhanced in the muscle of hypoglycemic and diabetic rats. Our studies demonstrated a functional disturbance in the neuronal glucose transporter GLUT3 in the cerebellum during insulin induced hypoglycemia in diabetic rats. Altered expression of muscarinic M1, M3 and α7nAchR and increased muscle AchE activity in hypoglycemic rats in cerebellum is suggested to cause cognitive and motor dysfunction. Hypoglycemia induced changes in ChAT and AchE gene expression is suggested to cause impaired acetycholine metabolism in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. The results shows that cerebellar cholinergic neurotransmission is impaired during hyperglycemia and hypoglycemia and the hypoglycemia is causing more prominent imbalance in cholinergic neurotransmission which is suggested to be a cause of cerebellar dysfunction associated with hypoglycemia. 相似文献
80.
Acetylcholine (ACh), the first neurotransmitter to be identified, regulate the activities of central and peripheral functions
through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR) have been implicated
in the pathophysiology of many major diseases of the central nervous system (CNS). Previous reports from our laboratory on
streptozotocin (STZ) induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus,
cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE) enzyme
activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic
rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one
of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum
that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal
velocity (Vmax) of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease
in maximal number (Bmax) and affinity (Kd) of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats.
We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with
insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal
with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum
and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors. 相似文献