全文获取类型
收费全文 | 5011篇 |
免费 | 334篇 |
国内免费 | 10篇 |
出版年
2023年 | 33篇 |
2022年 | 90篇 |
2021年 | 167篇 |
2020年 | 136篇 |
2019年 | 154篇 |
2018年 | 200篇 |
2017年 | 170篇 |
2016年 | 220篇 |
2015年 | 296篇 |
2014年 | 322篇 |
2013年 | 355篇 |
2012年 | 440篇 |
2011年 | 378篇 |
2010年 | 223篇 |
2009年 | 192篇 |
2008年 | 239篇 |
2007年 | 238篇 |
2006年 | 202篇 |
2005年 | 158篇 |
2004年 | 155篇 |
2003年 | 133篇 |
2002年 | 132篇 |
2001年 | 107篇 |
2000年 | 78篇 |
1999年 | 70篇 |
1998年 | 36篇 |
1997年 | 29篇 |
1996年 | 19篇 |
1995年 | 17篇 |
1994年 | 18篇 |
1993年 | 12篇 |
1992年 | 31篇 |
1991年 | 31篇 |
1990年 | 21篇 |
1989年 | 19篇 |
1988年 | 20篇 |
1987年 | 20篇 |
1986年 | 20篇 |
1985年 | 19篇 |
1984年 | 16篇 |
1983年 | 13篇 |
1982年 | 16篇 |
1981年 | 6篇 |
1980年 | 12篇 |
1979年 | 8篇 |
1978年 | 14篇 |
1977年 | 12篇 |
1976年 | 8篇 |
1974年 | 9篇 |
1968年 | 6篇 |
排序方式: 共有5355条查询结果,搜索用时 15 毫秒
991.
Nucleolar persistence during spermatogenesis of the genus Rhodnius (Hemiptera,Triatominae)
下载免费PDF全文
![点击此处可从《Cell biology international》网站下载免费的PDF全文](/ch/ext_images/free.gif)
992.
Waldemir Fernandes de Souza Leandro Augusto Barbosa Lijun Liu Wallace Martins de Araujo Julio Cesar Madureira de-Freitas-Junior Natalia Fortunato-Miranda Carlos Frederico Leite Fontes José Andrés Morgado-Díaz 《The Journal of membrane biology》2014,247(1):23-33
Studies have reported that Na,K-ATPase interacts with E-cadherin to stabilize (AJs) and regulate the expression of claudins, the main proteins present in the tight junction (TJ) in epithelial cells containing caveolae. However, the role of this ATPase in the regulation of the AJ and TJ proteins in colorectal cancer cells as well as the molecular events underlying this event in a caveolae-independent system remain undefined. In the present study, we used ouabain, a classic drug known to inhibit Na,K-ATPase, and Caco-2 cells, which are a well-established human colorectal cancer model that does not exhibit caveolae. We demonstrated that ouabain treatment resulted in a reduction of the β1 Na,K-ATPase protein and cell redistribution of the AJ proteins E-cadherin and β-catenin, as well as the α1 Na,K-ATPase subunit. Furthermore, ouabain increased claudin-3 protein levels, impaired the TJ barrier function and increased cell viability and proliferation during the early stages of treatment. Additionally, the observed ouabain-induced events were dependent on the activation of ERK1/2 signaling; but in contrast to previous studies, this signaling cascade was caveolae-independent. In conclusion, our findings strongly suggest that α1 and β1 Na,K-ATPase downregulation and ERK1/2 activation induced by ouabain are interlinked events that play an important role during cell–cell adhesion loss, which is an important step during the tumor progression of colorectal carcinomas. 相似文献
993.
Guilherme Henrique Souza Bomfim Luciana Ferreira Verde Roberto Frussa-FilhoAron Jurkiewicz Neide Hyppolito Jurkiewicz 《Life sciences》2014
Aims
Alcohol withdrawal syndrome (AWS) is characterized by a set of physiological modifications triggered by abrupt withdrawal and/or decreasing consumption of ethanol (EtOH), which may manifest 16–48 h after ceasing consumption. The relationship between the effects of AWS and central and peripheral sympathetic neurotransmission is unknown. This study investigates the possible mechanisms on the sympathetic system during periods of AWS.Main methods
Male Wistar rats were treated with EtOH (6–10 g/kg/day/v.o. 5 days). Subsequently, 1 h, 24 h, 48 h and 120 h after administration of the last dose of EtOH, the animals were sacrificed, and their vas deferens (VD) were removed to perform the following evaluations: (a) concentration–effect curves of sympathetic agonist; (b) activity of α2-adrenoreceptor; (c) function of voltage-dependent calcium channels (Cav); and (d) release of endogenous catecholamines measured in real time coupled to HPLC.Key findings
The results showed that the maximum effects of contraction were increased by agonists tested in at 24 h and 48 h EtOH withdrawal. The inhibitory affinity (pIC50) of guanfacine was decreased 24 h EtOH withdrawal. The function of Cav was also decreased as pIC50 values dropped 24 h and 48 h EtOH withdrawal. The release of catecholamines increased 48 h after EtOH withdrawal. It is suggested that AWS triggers hyperactivity in peripheral sympathetic neurotransmission.Significance
The mechanisms underlying hyperactivity are possibly explained by a failure of autoregulation from catecholamines released by α2-adrenoreceptors and/or an increase of Cav function, which may be potential targets to attenuate the symptoms of AWS at the peripheral level. 相似文献994.
Fabiana P.M. Schiavon Any de Castro Ruiz Marques Marcia A. Carrara Helenir Medri de Souza Christiano Rodrigues Schamber Rui Curi Roberto B. Bazotte 《Life sciences》2014
Aims
Liver glycogen catabolism was evaluated in male Swiss mice fed a high-fat diet rich in saturated fatty acids (HFD) or normal fat diet (NFD) during one week.Main methods
Liver glycogenolysis (LG) and liver glucose production (LGP) were measured either under basal or stimulated conditions (infusion of glycogenolytic agents). Thus, isolated perfused livers from HFD and NFD mice were infused with glycogenolytic agents, i.e., glucagon, epinephrine, phenylephrine, isoproterenol, adenosine-3′-5′-cyclic monophosphate (cAMP), N6,2′-O-dibutyryl-cAMP (DB-cAMP), 8-bromoadenosine-cAMP (8-Br-cAMP) or N6-monobutyryl-cAMP (N6-MB-cAMP). Moreover, glycemia and liver glycogen content were measured.Key findings
Glycemia, liver glycogen content and basal rate of LGP and LG were not influenced by the HFD. However, LGP and LG were lower (p < 0.05) in HFD mice during the infusions of glucagon (1 nM), epinephrine (20 μM) or phenylephrine (20 μM). In contrast, the activation of LGP and LG during the infusion of isoproterenol (20 μM) was not different (HFD vs. NFD). Because glucagon showed the most prominent response, the effect of cAMP, its intracellular mediator, on LGP and LG was investigated. cAMP (150 μM) showed lower activation of LGP and LG in the HFD group. However, the activation of LGP and LG was not influenced by HFD whether DB-cAMP (3 μM), 8-Br-cAMP (3 μM) or N6-MB-cAMP (3 μM) were used.Significance
The activation of LGP and LG depends on the intracellular availability of cAMP. It can be concluded that cAMP played a pivotal role on the activation of LG in high-fat diet fed mice. 相似文献995.
Juliana Falcato Vecina Alexandre Gabarra Oliveira Tiago Gomes Araujo Sueli Regina Baggio Cristiane Okuda Torello Mario Jose Abdalla Saad Mary Luci de Souza Queiroz 《Life sciences》2014
Aims
The search for natural agents that minimize obesity-associated disorders is receiving special attention. In this regard, the present study aimed to evaluate the prophylactic effect of Chlorella vulgaris (CV) on body weight, lipid profile, blood glucose and insulin signaling in liver, skeletal muscle and adipose tissue of diet-induced obese mice.Main methods
Balb/C mice were fed either with standard rodent chow diet or high-fat diet (HFD) and received concomitant treatment with CV for 12 consecutive weeks. Triglyceride, free fatty acid, total cholesterol and fractions of cholesterol were measured using commercial assay. Insulin and leptin levels were determined by enzyme-linked immunosorbent assay (ELISA). Insulin and glucose tolerance tests were performed. The expression and phosphorylation of IRβ, IRS-1 and Akt were determined by Western blot analyses.Key findings
Herein we demonstrate for the first time in the literature that prevention by CV of high-fat diet-induced insulin resistance in obese mice, as shown by increased glucose and insulin tolerance, is in part due to the improvement in the insulin signaling pathway at its main target tissues, by increasing the phosphorylation levels of proteins such as IR, IRS-1 and Akt. In parallel, the lower phosphorylation levels of IRS-1ser307 were observed in obese mice. We also found that CV administration prevents high-fat diet-induced dyslipidemia by reducing triglyceride, cholesterol and free fatty acid levels.Significance
We propose that the modulatory effect of CV treatment preventing the deleterious effects induced by high-fat diet is a good indicator for its use as a prophylactic–therapeutic agent against obesity-related complications. 相似文献996.
Eliane Soler Parra Natalia Baratella Panzoldo Vanessa Helena de Souza Zago Daniel Zanetti Scherrer Fernanda Alexandre Jamal Bakkarat Valeria Sutti Nunes Edna Regina Nakandakare Eder Carlos Rocha Quint?o Wilson Nadruz-Jr Eliana Cotta de Faria Andrei C. Sposito 《PloS one》2014,9(12)
Background
Misclassification of patients as low cardiovascular risk (LCR) remains a major concern and challenges the efficacy of traditional risk markers. Due to its strong association with cholesterol acceptor capacity, high-density lipoprotein (HDL) size has been appointed as a potential risk marker. Hence, we investigate whether HDL size improves the predictive value of HDL-cholesterol in the identification of carotid atherosclerotic burden in individuals stratified to be at LCR.Methods and Findings
284 individuals (40–75 years) classified as LCR by the current US guidelines were selected in a three-step procedure from primary care centers of the cities of Campinas and Americana, SP, Brazil. Apolipoprotein B-containing lipoproteins were precipitated by polyethylene glycol and HDL size was measured by dynamic light scattering (DLS) technique. Participants were classified in tertiles of HDL size (<7.57; 7.57–8.22; >8.22 nm). Carotid intima-media thickness (cIMT) <0.90 mm (80th percentile) was determined by high resolution ultrasonography and multivariate ordinal regression models were used to assess the association between cIMT across HDL size and levels of lipid parameters. HDL-cholesterol was not associated with cIMT. In contrast, HDL size >8.22 nm was independently associated with low cIMT in either unadjusted and adjusted models for age, gender and Homeostasis Model Assessment 2 index for insulin sensitivity, ethnicity and body mass index (Odds ratio 0.23; 95% confidence interval 0.07–0.74, p = 0.013).Conclusion
The mean HDL size estimated with DLS constitutes a better predictor for subclinical carotid atherosclerosis than the conventional measurements of plasma HDL-cholesterol in individuals classified as LCR. 相似文献997.
Dayvison Francis Saraiva Freitas Antonio Carlos Francesconi do Valle Margarete Bernardo Tavares da Silva Dayse Pereira Campos Marcelo Rosandiski Lyra Rogerio Valls de Souza Valdiléa Gon?alves Veloso Rosely Maria Zancopé-Oliveira Francisco Inácio Bastos Maria Clara Gutierrez Galhardo 《PLoS neglected tropical diseases》2014,8(8)
Sporotrichosis associated with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil, affecting a large at-risk population, which includes HIV-infected individuals. We assessed patients co-infected by Sporothrix spp. and HIV over time in the context of an unabated sporotrichosis epidemic.A retrospective cohort retrieved information from a National reference institute for infectious diseases regarding 48 patients with sporotrichosis-HIV co-infection (group 1) as well as 3,570 patients with sporotrichosis (group 2), from 1987 through March 2013. Most patients from group 1 were male (68.8%), whereas women were predominant in group 2 (69.1%; p<0.0001). Patients from group 1 were younger than those from group 2 (μ = 38.38±10.17 vs. 46.34±15.85; p<0.001) and differed from group 2 in terms of their race/ethnic background, with 70.8% non-white patients in group 1 vs. 38.6% from group 2 (p<0.0001). Close to half (∼44%) of the patients from group 1 were hospitalized due to sporotrichosis over time, whereas hospitalization was very unlikely in group 2, among whom approximately 1% were hospitalized over time. Dissemination of sporotrichosis was the main cause of hospitalization in both groups, although it was more common among hospitalized patients from group 1 (19/21 [90.5%] vs. 16/37 [43.2%]; p<0.001). Over the period under analysis, eight patients died due to sporotrichosis (3/48 vs. 5/3,570). The diagnosis of sporotrichosis elicited HIV testing and subsequent diagnosis in 19/48 patients, whereas 23/48 patients were simultaneously diagnosed with the two infections.HIV infection aggravates sporotrichosis, with a higher incidence of severe disseminated cases and a higher number of hospitalizations and deaths. Underserved populations, among whom sporotrichosis has been propagated, have been affected by different transmissible (e.g., HIV) and non-transmissible diseases. These populations should be targeted by community development programs and entitled to integrated management and care of their superimposed burdens. 相似文献
998.
Gabriela Vaz Meirelles Arina Marina Perez Edmárcia Elisa de Souza Ferna Luisa Basei Priscila Ferreira Papa Talita Diniz Melo Hanchuk Vanessa Bomfim Cardoso Jrg Kobarg 《World journal of biological chemistry》2014,5(2):141-160
Aside from Polo and Aurora, a third but less studied kinase family involved in mitosis regulation is the never in mitosis-gene A(NIMA)-related kinases(Neks). The founding member of this family is the sole member NIMA of Aspergillus nidulans, which is crucial for the initiation of mitosis in that organism. All 11 human Neks have been functionally assigned to one of the three core functions established for this family in mammals:(1) centrioles/mitosis;(2) primary ciliary function/ciliopathies; and(3) DNA damage response(DDR). Recent findings, especially on Nek 1 and 8, showed however, that several Neks participate in parallel in at least two of these contexts: primary ciliary function and DDR. In the core section of this in-depth review, we report the current detailed functional knowledge on each of the 11 Neks. In the discussion, we return to the cross-connections among Neks and point out how our and other groups' functional and interactomics studies revealed that most Neks interact with protein partners associated with two if not all three of the functional contexts. We then raise the hypothesis that Neks may be the connecting regulatory elements that allow the cell to fine tune and synchronize the cellular events associated with these three core functions. The new and exciting findings on the Nek family open new perspectives and should allow the Neks to finally claim the attention they deserve in the field of kinases and cell cycle biology. 相似文献
999.
Bianca Silva Vieira de Souza Karla Christina Sousa Silva Ana Flávia Alves Parente Clayton Luiz Borges Juliano Domiraci Paccez Maristela Pereira Célia Maria de Almeida Soares Marcia Giambiagi-deMarval Mirelle Garcia Silva-Bailão Juliana Alves Parente-Rocha 《Microbes and infection / Institut Pasteur》2019,21(10):456-463
Staphylococcus saprophyticus is a gram-positive coagulase negative bacteria which shows clinical importance due to its capability of causing urinary tract infections (UTI), as well as its ability to persist in this environment. Little is known about how S. saprophyticus adapts to the pH shift that occurs during infection. Thus, in this study we aim to use a proteomic approach to analyze the metabolic adaptations which occur as a response by S. saprophyticus when exposed to acid (5.5) and alkaline (9.0) pH environments. Proteins related to iron storage are overexpressed in acid pH, whilst iron acquisition proteins are overexpressed in alkaline pH. It likely occurs because iron is soluble at acid pH and insoluble at alkaline pH. To evaluate if S. saprophyticus synthesizes siderophores, CAS assays were performed, and the results confirmed their production. The chemical characterization of siderophores demonstrates that S. saprophyticus produces carboxylates derived from citrate. Of special note is the fact that citrate synthase (CS) is down-regulated during incubation at acid pH, corroborating this result. This data was also confirmed by enzymatic assay. Our results demonstrate that iron metabolism regulation is influenced by different pH levels, and show, for the first time, the production of siderophores by S. saprophyticus. Enzymatic assays suggest that citrate from the tricarboxylic acid cycle (TCA) is used as substrate for siderophore production. 相似文献
1000.
Antunes Daiane Felberg de Souza Junior Cláudio Galvão de Morais Junior Marcos Antonio 《World journal of microbiology & biotechnology》2000,16(7):653-654
Efficient plasmid transformation of Kluyveromyces marxianus cells of 1.9 × 103 transformant μg−1 DNA with an episomal plasmid was achieved by the use of a simple lithium acetate method with the addition of 10 mM DTT and
an increased heat shock temperature of 47 °C. This method is shown to be also efficient for replicative plasmids. Therefore,
we suggest its use as a routine method to transform K. marxianus cells.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献