全文获取类型
收费全文 | 2145篇 |
免费 | 151篇 |
国内免费 | 109篇 |
出版年
2023年 | 60篇 |
2022年 | 69篇 |
2021年 | 77篇 |
2020年 | 54篇 |
2019年 | 74篇 |
2018年 | 85篇 |
2017年 | 43篇 |
2016年 | 55篇 |
2015年 | 55篇 |
2014年 | 142篇 |
2013年 | 149篇 |
2012年 | 86篇 |
2011年 | 111篇 |
2010年 | 96篇 |
2009年 | 102篇 |
2008年 | 85篇 |
2007年 | 128篇 |
2006年 | 92篇 |
2005年 | 80篇 |
2004年 | 61篇 |
2003年 | 67篇 |
2002年 | 50篇 |
2001年 | 37篇 |
2000年 | 41篇 |
1999年 | 28篇 |
1998年 | 32篇 |
1997年 | 33篇 |
1996年 | 20篇 |
1995年 | 28篇 |
1994年 | 20篇 |
1993年 | 16篇 |
1992年 | 19篇 |
1991年 | 24篇 |
1990年 | 16篇 |
1989年 | 19篇 |
1988年 | 10篇 |
1987年 | 14篇 |
1986年 | 8篇 |
1985年 | 20篇 |
1984年 | 28篇 |
1983年 | 15篇 |
1982年 | 26篇 |
1981年 | 20篇 |
1980年 | 21篇 |
1979年 | 18篇 |
1978年 | 16篇 |
1977年 | 13篇 |
1976年 | 17篇 |
1975年 | 6篇 |
1973年 | 6篇 |
排序方式: 共有2405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.
《Journal of molecular biology》2021,433(21):167224
Retinoblastoma-binding protein 1 (RBBP1) is involved in gene regulation, epigenetic regulation, and disease processes. RBBP1 contains five domains with DNA-binding or histone-binding activities, but how RBBP1 specifically recognizes chromatin is still unknown. An AT-rich interaction domain (ARID) in RBBP1 was proposed to be the key region for DNA-binding and gene suppression. Here, we first determined the solution structure of a tandem PWWP-ARID domain mutant of RBBP1 after deletion of a long flexible acidic loop L12 in the ARID domain. NMR titration results indicated that the ARID domain interacts with DNA with no GC- or AT-rich preference. Surprisingly, we found that the loop L12 binds to the DNA-binding region of the ARID domain as a DNA mimic and inhibits DNA binding. The loop L12 can also bind weakly to the Tudor and chromobarrel domains of RBBP1, but binds more strongly to the DNA-binding region of the histone H2A-H2B heterodimer. Furthermore, both the loop L12 and DNA can enhance the binding of the chromobarrel domain to H3K4me3 and H4K20me3. Based on these results, we propose a model of chromatin recognition by RBBP1, which highlights the unexpected multiple key roles of the disordered acidic loop L12 in the specific binding of RBBP1 to chromatin. 相似文献
3.
A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men
《Endocrine practice》2021,27(12):1225-1231
ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS. 相似文献
4.
Parvinder Kaur 《Biometrical journal. Biometrische Zeitschrift》1985,27(1):107-110
For the estimation of population mean in simple random sampling, an efficient regression-type estimator is proposed which is more efficient than the conventional regression estimator and hence than mean per unit estimator, ratio and product estimators and many other estimators proposed by various authors. Some numerical examples are included for illustration. 相似文献
5.
6.
Th. Wurm C. Albers 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1989,159(3):255-261
Summary The interaction of allosteric effectors (CO2, ATP, H+) with respect to the oxygen affinity of carp hemoglobin was analyzed by determining oxygen binding curves spectrophotometrically in dilute solutions of stripped hemoglobin at 20°C. The pH range studied was 6.8–8.2.P
CO2 was 0, 10 and 70 mmHg (0, 1.33 and 9.3 kPa). ATP/Hb4 was 0, 8 and 24. In the presence of either CO2 or ATP, the effects of the cofactors onP
50 were as expected over the whole pH range. In contrast to other published data, each cofactor also had a significant effect onP
50 in the presence of the other cofactor. Evidence was obtained that oxylabile carbamate is formed by carp hemoglobin and that the formation of carbamate persists at a lower level in the presence of ATP. The results support the view that the binding of ATP to carp hemoglobin requires only one terminal amino group, leaving the other N-terminal of the -chain free to react with CO2. 相似文献
7.
心房钠尿因子对麻醉家兔局部血流的影响 总被引:3,自引:2,他引:1
在42只麻醉家兔,观察了静脉注射心房肽Ⅱ(AtriopeptinⅡ,APⅡ)对局部血流量以及动脉内注射 AP Ⅱ 对局部血管阻力的影响。结果如下:(1)静脉注射 APⅡ(30μg/kg)5min后,平均动脉压(MAP)降低11.0±1.5mmHg(n=8,M±SE,下同),与溶剂对照组相比有明显差异(P相似文献
8.
甘蓝型油菜芥酸和二十碳烯酸含量的基因效应 总被引:3,自引:0,他引:3
以甘蓝型油菜的4种纯合芥酸基因型之间所有可能的6个杂交组合的P_1、P_2、F_1、P_2、B_1和B_2世代为材料,用生统遗传学方法研究了芥酸和二十碳烯酸的基因作用形式及效应。发现无论亲本是单基因差异还是二基因差异,F_1和F_2代的芥酸含量都接近中亲值,F_1略大于中亲值和F_(20)世代均值分析表明,芥酸含量的遗传符合加性显性模型,加性效应占绝对优势,显性效应不显著。用数量遗传学方法估计的芥酸基因数与已知的结果相近。 相似文献
9.
10.
朱景德 《分子细胞生物学报》1988,(4)
我采用点杂交的方法,对人β型血珠蛋白基因簇的染色质结构与基因转录活性之间的关系进行了研究。以对DNase Ⅰ消化的敏感性作为染色质的结构参数,我将β型血珠蛋白基因簇中11个区域之间以及其与不表达基因区(乳糖白蛋白和免疫球蛋白不变区λ轻链基因)的染色结构进行比较。实验的细胞系统为K 562红白血病细胞与人胚皮肤细胞株(HES)。所获得的结果提示,在细胞核内,表达基因的染色质结构疏松,对DNase Ⅰ消化的敏感性远较不表达基因区的为高。此外,本文还对有关点杂交的方法学问题进行了较为详尽的讨论。 相似文献