全文获取类型
收费全文 | 2434篇 |
免费 | 183篇 |
专业分类
2617篇 |
出版年
2023年 | 20篇 |
2022年 | 44篇 |
2021年 | 72篇 |
2020年 | 68篇 |
2019年 | 70篇 |
2018年 | 97篇 |
2017年 | 68篇 |
2016年 | 108篇 |
2015年 | 143篇 |
2014年 | 132篇 |
2013年 | 192篇 |
2012年 | 193篇 |
2011年 | 179篇 |
2010年 | 103篇 |
2009年 | 104篇 |
2008年 | 127篇 |
2007年 | 119篇 |
2006年 | 108篇 |
2005年 | 112篇 |
2004年 | 82篇 |
2003年 | 65篇 |
2002年 | 80篇 |
2001年 | 46篇 |
2000年 | 24篇 |
1999年 | 25篇 |
1998年 | 16篇 |
1997年 | 10篇 |
1996年 | 15篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 11篇 |
1992年 | 14篇 |
1991年 | 8篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 11篇 |
1987年 | 11篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 13篇 |
1982年 | 4篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 7篇 |
1977年 | 7篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 5篇 |
1968年 | 6篇 |
排序方式: 共有2617条查询结果,搜索用时 0 毫秒
101.
Calliari LE Longui CA Rocha MN Faria CD Kochi C Melo MR Melo MB Monte O 《Genetics and molecular research : GMR》2007,6(2):277-283
Adrenal hypoplasia congenita (AHC) is a rare disease that can be caused by many abnormalities, including an X-linked form. Mutations in the DAX1 gene have been assigned as the genetic cause of AHC. We describe here three siblings with AHC, clinically presented at different ages, two in the neonatal period and one oligosymptomatic during infancy. Molecular analysis was able to detect a novel mutation in exon 1 of the DAX1 gene, consisting of a transition of C to T at position 359, determining a stop codon at position 359 (Q359X). The mutated gene encodes a truncated protein missing a large portion of the ligand-binding domain (C-terminal domain). The recognition of the disease in the index case suggested the diagnosis in the other siblings. Interestingly, the same mutation is presented with different phenotypes, suggesting that first-degree family members of patients with DAX1 mutations should be carefully evaluated routinely. 相似文献
102.
Decline in self-renewal factors contributes to aging of the stem cell niche in the Drosophila testis 总被引:2,自引:0,他引:2
Aging is characterized by compromised organ and tissue function. A decrease in stem cell number and/or activity could lead to the aging-related decline in tissue homeostasis. We have analyzed how the process of aging affects germ line stem cell (GSC) behavior in the Drosophila testis and report that significant changes within the stem cell microenvironment, or niche, occur that contribute to a decline in stem cell number over time. Specifically, somatic niche cells in testes from older males display reduced expression of the cell adhesion molecule DE-cadherin and a key self-renewal signal unpaired (upd). Loss of upd correlates with an overall decrease in stem cells residing within the niche. Conversely, forced expression of upd within niche cells maintains GSCs in older males. Therefore, our data indicate that age-related changes within stem cell niches may be a significant contributing factor to reduced tissue homeostasis and regeneration in older individuals. 相似文献
103.
Rocha DD Dantas IN Albuquerque MR Montenegro RC Pessoa C de Moraes MO Pessoa OD Silveira ER Costa-Lotufo LV 《化学与生物多样性》2007,4(12):2835-2844
A detailed study on the cytotoxic effects of five known constituents isolated from the flowers and roots of Eupatorium betonicaeforme is reported, including 2,2-dimethyl-6-vinylchroman-4-one (1), 2-senecioyl-4-vinylphenol (2), 6-acetyl-2,2-dimethylchroman-4-one (3), (4E)-8beta-angeloyloxy-9beta,10beta-dihydroxy-1-oxogermacra-4,11(13)-dien-12,6alpha-olide (4), and 3beta-hydroxyicosan-1,5beta-olide (5). The sesquiterpene lactone 4 exhibited the highest cytotoxicity, with IC50 values ranging from 3.9 to 9.9 microM, showing some degree of cell selectivity. The antiproliferative activity of 4 was examined towards HL-60 cells, and found to diminish cell viability in a dose-dependent manner. Moreover, at all concentrations tested, there was a decrease in the number of cells capable of incorporating 5-bromo-2'-deoxyuridine (BrdU), indicating disruption of DNA synthesis. The morphological changes induced by 4 were compatible with apoptotic cell death. This work, thus, corroborates the anticancer potential of Eupatorium secondary metabolites. 相似文献
104.
Morphogenesis control in Candida albicans and Candida dubliniensis through signaling molecules produced by planktonic and biofilm cells 总被引:1,自引:0,他引:1 下载免费PDF全文
Martins M Henriques M Azeredo J Rocha SM Coimbra MA Oliveira R 《Eukaryotic cell》2007,6(12):2429-2436
Morphogenesis control by chemical signaling molecules is beginning to be highlighted in Candida biology. The present study focuses on morphogenic compounds produced in situ by Candida albicans and Candida dubliniensis during planktonic and biofilm growth that may at least partially substantiate the effect promoted by supernatants in morphogenesis. For both species, planktonic versus biofilm supernatants were analyzed by headspace-solid-phase microextraction and gas chromatography-mass spectrometry. Both planktonic cells and biofilm supernatants of C. albicans and C. dubliniensis contained isoamyl alcohol, 2-phenylethanol, 1-dodecanol, E-nerolidol, and E,E-farnesol. Alcohol secretion profiles were species, culture mode, and growth time specific. The addition of exogenous alcohols to the cultures of both species inhibited the morphological transition from the yeast to the filamentous form by up to 50%. The physiological role of these alcohols was put to evidence by comparing the effects of a 96-h cultured supernatant with synthetic mixtures containing isoamyl alcohol, 2-phenylethanol, E-nerolidol, and E,E-farnesol at concentrations determined herein. All synthetic mixtures elicited a morphological effect similar to that observed for the corresponding supernatants when used to treat C. albicans and C. dubliniensis cultures, except for the effect of the 96-h C. dubliniensis planktonic supernatant culture on C. albicans. Overall, these results reveal a group of alcohol extracellular signaling molecules that are biologically active with C. albicans and C. dubliniensis morphogenesis. 相似文献
105.
Duarte MM Loro VL Rocha JB Leal DB Bem AF Dorneles A Morsch VM Schetinger MR 《The FEBS journal》2007,274(11):2707-2714
The activity of NTPDase (EC 3.6.1.5, apyrase, CD39) was verified in platelets from patients with increasing cholesterol levels. A possible association between cholesterol levels and inflammatory markers, such as oxidized low-density lipoprotein, highly sensitive C-reactive protein and oxidized low-density lipoprotein autoantibodies, was also investigated. Lipid peroxidation was estimated by measurement of thiobarbituric acid reactive substances in serum. The following groups were studied: group I, < 150 mg.dL(-1) cholesterol; group II, 151-200 mg.dL(-1) cholesterol; group III, 201-250 mg.dL(-1) cholesterol; and group IV, > 251 mg.dL(-1) cholesterol. The results demonstrated that both ATP hydrolysis and ADP hydrolysis were enhanced as a function of cholesterol level. Low-density lipoprotein levels increased concomitantly with total cholesterol levels. Triglyceride levels were increased in the groups with total cholesterol above 251 mg.dL(-1). Oxidized low-density lipoprotein levels were elevated in groups II, III, and IV. Highly sensitive C-reactive protein was elevated in the group with cholesterol levels higher than 251 mg.dL(-1). Oxidized low-density lipoprotein autoantibodies were elevated in groups III and IV. Thiobarbituric acid reactive substance content was enhanced as a function of cholesterol level. In summary, hypercholesterolemia is associated with enhancement of inflammatory response, oxidative stress, and ATP and ADP hydrolysis. The increased ATP and ADP hydrolysis in group IV was confirmed by an increase in CD39 expression on its surface. The increase in CD39 activity is possibly related to a compensatory response to the inflammatory and pro-oxidative state associated with hypercholesterolemia. 相似文献
106.
de Jesus Santana Mayla Barbosa-Júnior Sebastião Martins Dias Lana Laene Lima Silva Lázara Aline Simões da Silva Givanildo Zildo Fortini Evandro Alexandre Batista Diego Silva Otoni Wagner Campos da Costa Netto Antônio Paulino Rocha Diego Ismael 《In vitro cellular & developmental biology. Plant》2022,58(6):865-875
In Vitro Cellular & Developmental Biology - Plant - The aim of this study was to establish a system of in vitro germination and propagation of Guazuma ulmifolia Lam. microcuttings (Malvaceae).... 相似文献
107.
Sara Rocha Ricardo Ferraz Cristina Prudêncio Maria Helena Fernandes João Costa-Rodrigues 《Journal of cellular physiology》2019,234(11):19691-19701
Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue. 相似文献
108.
Lars Milke Patrícia Ferreira Nicolai Kallscheuer Adelaide Braga Michael Vogt Jannick Kappelmann Joana Oliveira Ana Rita Silva Isabel Rocha Michael Bott Stephan Noack Nuno Faria Jan Marienhagen 《Biotechnology and bioengineering》2019,116(6):1380-1391
In recent years microorganisms have been engineered towards synthesizing interesting plant polyphenols such as flavonoids and stilbenes from glucose. Currently, the low endogenous supply of malonyl-CoA, indispensable for plant polyphenol synthesis, impedes high product titers. Usually, limited malonyl-CoA availability during plant polyphenol production is avoided by supplementing fatty acid synthesis-inhibiting antibiotics such as cerulenin, which are known to increase the intracellular malonyl-CoA pool as a side effect. Motivated by the goal of microbial polyphenol synthesis being independent of such expensive additives, we used rational metabolic engineering approaches to modulate regulation of fatty acid synthesis and flux into the tricarboxylic acid cycle (TCA cycle) in Corynebacterium glutamicum strains capable of flavonoid and stilbene synthesis. Initial experiments showed that sole overexpression of genes coding for the native malonyl-CoA-forming acetyl-CoA carboxylase is not sufficient for increasing polyphenol production in C. glutamicum. Hence, the intracellular acetyl-CoA availability was also increased by reducing the flux into the TCA cycle through reduction of citrate synthase activity. In defined cultivation medium, the constructed C. glutamicum strains accumulated 24 mg·L −1 (0.088 mM) naringenin or 112 mg·L −1 (0.49 mM) resveratrol from glucose without supplementation of phenylpropanoid precursor molecules or any inhibitors of fatty acid synthesis. 相似文献
109.