全文获取类型
收费全文 | 7784篇 |
免费 | 569篇 |
国内免费 | 1篇 |
出版年
2023年 | 39篇 |
2022年 | 29篇 |
2021年 | 177篇 |
2020年 | 90篇 |
2019年 | 122篇 |
2018年 | 183篇 |
2017年 | 152篇 |
2016年 | 224篇 |
2015年 | 330篇 |
2014年 | 390篇 |
2013年 | 552篇 |
2012年 | 612篇 |
2011年 | 577篇 |
2010年 | 329篇 |
2009年 | 283篇 |
2008年 | 402篇 |
2007年 | 452篇 |
2006年 | 388篇 |
2005年 | 337篇 |
2004年 | 303篇 |
2003年 | 282篇 |
2002年 | 248篇 |
2001年 | 140篇 |
2000年 | 150篇 |
1999年 | 128篇 |
1998年 | 69篇 |
1997年 | 59篇 |
1996年 | 51篇 |
1995年 | 57篇 |
1994年 | 48篇 |
1993年 | 52篇 |
1992年 | 103篇 |
1991年 | 82篇 |
1990年 | 77篇 |
1989年 | 77篇 |
1988年 | 52篇 |
1987年 | 56篇 |
1986年 | 52篇 |
1985年 | 56篇 |
1984年 | 51篇 |
1983年 | 58篇 |
1982年 | 24篇 |
1981年 | 26篇 |
1979年 | 43篇 |
1978年 | 27篇 |
1975年 | 31篇 |
1974年 | 27篇 |
1973年 | 31篇 |
1970年 | 23篇 |
1967年 | 22篇 |
排序方式: 共有8354条查询结果,搜索用时 15 毫秒
1.
Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25 years, and lack of auto-antibodies. It accounts for 2–5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil. 相似文献
2.
Sashko Spassov Dietmar Pfeifer Karl Strosing Stefan Ryter Matthias Hummel Simone Faller Alexander Hoetzel 《PloS one》2014,9(7)
Recently, we have shown that inhalation of hydrogen sulfide (H2S) protects against ventilator-induced lung injury (VILI). In the present study, we aimed to determine the underlying molecular mechanisms of H2S-dependent lung protection by analyzing gene expression profiles in mice. C57BL/6 mice were subjected to spontaneous breathing or mechanical ventilation in the absence or presence of H2S (80 parts per million). Gene expression profiles were determined by microarray, sqRT-PCR and Western Blot analyses. The association of Atf3 in protection against VILI was confirmed with a Vivo-Morpholino knockout model. Mechanical ventilation caused a significant lung inflammation and damage that was prevented in the presence of H2S. Mechanical ventilation favoured the expression of genes involved in inflammation, leukocyte activation and chemotaxis. In contrast, ventilation with H2S activated genes involved in extracellular matrix remodelling, angiogenesis, inhibition of apoptosis, and inflammation. Amongst others, H2S administration induced Atf3, an anti-inflammatory and anti-apoptotic regulator. Morpholino mediated reduction of Atf3 resulted in elevated lung injury despite the presence of H2S. In conclusion, lung protection by H2S during mechanical ventilation is associated with down-regulation of genes related to oxidative stress and inflammation and up-regulation of anti-apoptotic and anti-inflammatory genes. Here we show that Atf3 is clearly involved in H2S mediated protection. 相似文献
3.
4.
5.
Adriana Calderaro Giovanna Piccolo Chiara Gorrini Sara Montecchini Sabina Rossi Maria Cristina Medici Carlo Chezzi Georges Snounou 《PloS one》2012,7(10)
It has been proposed that ovale malaria in humans is caused by two closely related but distinct species of malaria parasites: P. ovale curtisi and P. ovale wallikeri. We have extended and optimized a Real-time PCR assay targeting the parasite’s small subunit ribosomal RNA (ssrRNA) gene to detect both these species. When the assay was applied to 31 archival blood samples from patients diagnosed with P. ovale, it was found that the infection in 20 was due to P. ovale curtisi and in the remaining 11 to P. ovale wallikeri. Thus, this assay provides a useful tool that can be applied to epidemiological investigations of the two newly recognized distinct P. ovale species, that might reveal if these species also differ in their clinical manifestation, drugs susceptibility and relapse periodicity. The results presented confirm that P. ovale wallikeri is not confined to Southeast Asia, since the majority of the patients analyzed in this study had acquired their P. ovale infection in African countries, mostly situated in West Africa. 相似文献
6.
7.
M Magnani L Chiarantini E Vittoria U Mancini L Rossi A Fazi 《Biotechnology and applied biochemistry》1992,16(2):188-194
The use of adjuvants is usually required to induce strong immunological responses to protein antigens. However, in many cases these adjuvants cannot be extensively applied in human and veterinary vaccinations because of associated inflammatory reactions or granuloma formation. We show here that protein antigens (bovine serum albumin, hog liver uricase, and yeast hexokinase), coupled to autologous red blood cells by way of a biotin-avidin-biotin bridge, elicit an immunological response in mice similar to or higher than that obtained by the use of Freund's adjuvant. Quantities as low as 0.5 micrograms/mouse are high enough to generate these immunological responses. Furthermore, splenocytes of mice immunized by red blood cell-coupled antigens can be used to generate hybridomas secreting monoclonal antibodies. Thus, the delivery of antigens by autologous red blood cells is an effective way to avoid the use of adjuvants for producing anti-peptide antibodies and possibly to generate peptide vaccines. 相似文献
8.
9.
10.
Errors Related to Different Techniques of Intraperitoneal Injection in Mice 总被引:1,自引:0,他引:1 下载免费PDF全文
We found a 12% error in the placement of intraperitoneal injections of mice with the one-man procedure of injection. With a two-man procedure, the incidence of error was consistently reduced to 1.2%. 相似文献