全文获取类型
收费全文 | 1230篇 |
免费 | 91篇 |
出版年
2024年 | 2篇 |
2023年 | 7篇 |
2022年 | 13篇 |
2021年 | 25篇 |
2020年 | 16篇 |
2019年 | 17篇 |
2018年 | 22篇 |
2017年 | 32篇 |
2016年 | 55篇 |
2015年 | 51篇 |
2014年 | 72篇 |
2013年 | 101篇 |
2012年 | 91篇 |
2011年 | 99篇 |
2010年 | 53篇 |
2009年 | 47篇 |
2008年 | 76篇 |
2007年 | 72篇 |
2006年 | 78篇 |
2005年 | 70篇 |
2004年 | 57篇 |
2003年 | 50篇 |
2002年 | 50篇 |
2001年 | 17篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 10篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 6篇 |
1994年 | 5篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 2篇 |
1983年 | 7篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1976年 | 3篇 |
1974年 | 2篇 |
1967年 | 2篇 |
1965年 | 2篇 |
1939年 | 2篇 |
排序方式: 共有1321条查询结果,搜索用时 0 毫秒
991.
992.
993.
Mohan Krishnamoorthy Pragneshkumar Patel Mira Dimitrijevic Jonathan Dietrich Margaret Green Catherine Macken 《BMC bioinformatics》2011,12(1):51
Background
Large databases of genetic data are often biased in their representation. Thus, selection of genetic data with desired properties, such as evolutionary representation or shared genotypes, is problematic. Selection on the basis of epidemiological variables may not achieve the desired properties. Available automated approaches to the selection of influenza genetic data make a tradeoff between speed and simplicity on the one hand and control over quality and contents of the dataset on the other hand. A poorly chosen dataset may be detrimental to subsequent analyses. 相似文献994.
995.
Sla?ana Andrejevi? Peter Koro?ec Mira ?ilar Mitja Ko?nik Radovan Mijanovi? Branka Bona?i-Nikoli? Matija Rijavec 《PloS one》2015,10(11)
Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) is a rare autosomal dominant disease characterized by recurrent life-threatening oedemas and/or abdominal pain and caused by mutations affecting the C1 inhibitor gene, SERPING1. We sought to investigate the spectrum of SERPING1 mutations in Serbia and the possible genotype-phenotype association. C1-INH-HAE was diagnosed on the basis of clinical and laboratory criteria in 40 patients from 27 families; four were asymptomatic. Mutational analysis of the SERPING1 gene was performed by sequencing and multiplex ligation-dependent probe amplification. Disease-causing mutations in SERPING1 were identified in all patients. In C1-INH-HAE type I, we identified 19 different mutations, including 6 missense mutations, 6 nonsense mutations, 2 small deletions, 1 small insertion, 2 splicing defects and 2 large deletions. Two of the mutations (c.300C>T and c.1184_1185insTA) are reported here for the first time. All C1-INH-HAE type II patients from three families harboured the same substitution (c.1396C>T). Based on the type of mutation identified in the SERPING1 gene, patients were divided into two groups: group 1 (nonsense, frameshift, large deletions/insertions, splicing defect, and mutations at Arg444) or group 2 (missense, excluding mutations at Arg444). Significant differences were found in the clinical severity score (P = 0.005), prevalence of laryngeal (P = 0.040) and facial (P = 0.013) oedema, and long-term prophylaxis (P = 0.023) between the groups with different types of mutations. Because our population consisted of related subjects, differences in the severity score between mutation groups were further confirmed using the generalized estimating equation (P = 0.038). Our study identified 20 different disease-causing mutations, including two novel mutations, in all C1-INH-HAE patients, highlighting the heterogeneity of mutations in the SERPING1 gene. Furthermore, it appears that mutations with a clear effect on C1-INH function might be responsible for a more severe disease phenotype. 相似文献
996.
Sanna Niinivehmas Pekka A. Postila Sanna Rauhamäki Elangovan Manivannan Sami Kortet Mira Ahinko 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):743-754
A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-β-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced ≥62% HSD1 inhibition at 5?µM and, furthermore, three of them produced ≥68% inhibition at 1?µM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-β-hydroxysteroid dehydrogenase 2 – a requirement for lowering effective oestradiol levels in vivo. Moreover, the analysis led to the synthesis and discovery of 3-imidazolecoumarin as a potent aromatase inhibitor. In short, coumarin core can be tailored with specific ring and polar moiety substitutions to block either the sulphatase pathway or the aromatase pathway for treating breast cancer and endometriosis. 相似文献
997.
998.
Danilo Ercolini Francesca De Filippis Antonietta La Storia Michele Iacono 《Applied and environmental microbiology》2012,78(22):8142-8145
Intermediates of production of two batches of traditional mozzarella cheese were analyzed by culture-independent pyrosequencing. The quantitative distribution of taxa within the samples suggested that thermophilic lactic acid bacteria from the natural starter were mainly responsible for the fermentation, while microorganisms found in raw milk did not develop during fermentation. 相似文献
999.
We investigated homologous and heterologous downregulation of FSH receptor mRNA in porcine granulosa cells from ovaries of immature pigs. Cultures were treated with 0, 40, or 200 ng/ml porcine FSH or medium and terminated at 24 hr intervals for Northern analysis of FSH receptor and cytochrome P450 side chain cleavage (P450scc) mRNA, and for radioimmunoassay of progesterone. Cells luteinized over 96 hr, and control cultures displayed increases in P450scc (8–10 fold) and FSH receptor (2 fold) mRNA and progesterone (100 fold). FSH reduced FSH receptor mRNA by 50–90%, increased P450scc mRNA 8 fold within 48 hr, and elevated progesterone logarithmically over 96 hr. Luteinized cells, (after 96 hr) received FSH or LH (1–200 ng/ml) or prostaglandin E2 (0.01–1.0 mg/ml) for 6 hr resulting in increased P450scc mRNA (2–8 fold), and progesterone (2–5 fold), and reduced FSH receptor mRNA. FSH (200 ng/ml) or the cAMP analog, dbcAMP (1 mM) for 0–24 hr reduced FSH receptor mRNA to 15% of control from 4–24 hr and elevated P450scc mRNA at 4 and 6 hr, respectively, to maxima at 12–24 hr. Forskolin (1–10 mM) increased P450scc mRNA (2–3 fold) and downregulated FSH receptor mRNA, effects reversed by the inhibitor of cAMP, rpcAMPs. Both epidermal growth factor, and the activator of the protein kinase C pathway, phorbol 12‐myristate, 13‐acetate (PMA) at 10 nM reduced FSH receptor mRNA. We conclude that downregulation of FSH receptor mRNA in luteinized granulosa cells is mediated by both homologous and heterologous ligands which employ cAMP, and that growth factors that activate the PKC pathway reduce FSH receptor and P450scc mRNA abundance. Mol. Reprod. Dev. 53:198–207, 1999. © 1999 Wiley‐Liss, Inc. 相似文献
1000.
Propranolol, a β-adrenergic receptor blocker, is found to induce polyspermy in sea urchin eggs. Unfertilized sea urchin eggs treated for 10 min with 50 μM of propranolol, and then inseminated, become polyspermic and show a fertilization envelope which is barely visible to the light microscope. Examination of treated eggs by transmission and scanning electron microscopy shows that the drug does not alter the cortex of the unfertilized egg. However, after insemination an incomplete cortical reaction occurs. This might well account for both polyspermy and the defective elevation of the fertilization envelope. Since the effects of the drug are reversed by simultaneous treatment with adrenalin, perhaps propranolol interferes with the monoaminergic system that has been proposed to be active. The involvement of the monoaminergic system in the fertilization process is present in the sea urchin egg. © 1996 Wiley-Liss, Inc. 相似文献