全文获取类型
收费全文 | 1504篇 |
免费 | 94篇 |
国内免费 | 2篇 |
出版年
2023年 | 12篇 |
2022年 | 34篇 |
2021年 | 62篇 |
2020年 | 65篇 |
2019年 | 118篇 |
2018年 | 117篇 |
2017年 | 59篇 |
2016年 | 71篇 |
2015年 | 71篇 |
2014年 | 106篇 |
2013年 | 143篇 |
2012年 | 128篇 |
2011年 | 125篇 |
2010年 | 74篇 |
2009年 | 64篇 |
2008年 | 56篇 |
2007年 | 61篇 |
2006年 | 38篇 |
2005年 | 25篇 |
2004年 | 34篇 |
2003年 | 23篇 |
2002年 | 19篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1972年 | 2篇 |
1968年 | 3篇 |
1945年 | 1篇 |
排序方式: 共有1600条查询结果,搜索用时 687 毫秒
961.
Mehdi Rahimmalek Badraldin Ebrahim Sayed Tabatabaei Ahmad Arzani Mojtaba Khorrami 《Genes & genomics.》2011,33(5):475-482
Yarrow (Achillea millefoilum L.) is an important medicinal plant with different medicinal and ornamental uses. In this study, SSR markers were developed for the first time from the genome A. millefolium using the slightly modified Hamilton protocol. Three yarrow genomic libraries were constructed, enriched for microsatellite motifs AG, AC and ATG. A total of 30 primer pairs were developed of which 16 were polymorphic in 26 A. millefolium accessions. One accession from A. tenuifolia species was also included to assess the transferability of new developed SSR primers in other species. The average allele number of SSR markers was 8.5 per locus and ranged from 2 to 14. The observed heterozygosity (H O) varied from 0 to 0.96 with an average of 0.52 and the expected heterozygosity (H E) ranged from 0.07 to 0.49 with an average of 0.39. Among primers, Am142 showed the highest polymorphic information content (PIC) and the lowest value was obtained from Am59 primer with an average of 0.33. Three loci (AmK59, AmK344 and AmK329) deviated significantly from Hardy-Wrinberg Equlibrium (HWE) and one locus (Am344) might have null alleles. Cluster and PCoA analyses classified A. millefolium accessions according to their geographical distribution and A. tenuifolia species completely separated from A. millefoliulm genotypes. 相似文献
962.
Makoolati Z Movahedin M Forouzandeh-Moghadam M 《In vitro cellular & developmental biology. Animal》2011,47(5-6):391-398
Presence of specific growth factors and feeder layers are thought to be important for in vitro embryonic stem cell (ESCs) differentiation. In this study, the effect of bone morphogenetic protein 4 (BMP4) and mouse embryonic fibroblasts (MEFs) co-culture system on germ cell differentiation from mouse ESCs was evaluated. One-day-old embryoid body was cultured for 4?d in simple culture systems or on top of the MEFs, both in the presence or absence of BMP4. Data showed significant higher viability percent and proliferation rate in simple culture media compared to co-culture systems. Analysis of gene expression indicated that the germ cell-specific genes (VASA and Stra8) were expressed in a significant higher ratio in BMP4-treated cells in simple culture system. Also, the results of immunocytochemistry in simple culture systems showed that the mean percentage of immunostaining cells of VASA, the primordial germ cell (PGC) marker, was increased significantly in BMP4-treated cells compared with BMP4-free group. Meanwhile, CDH1, the late premiotic germ cell marker, showed no significant difference between these two groups. The results suggest that BMP4 is an efficient inducer in PGC derivation from mouse ESC. However, the employment of MEFs as feeder has no apparent effect on PGC derivation. 相似文献
963.
It seems that IL-18 has a crucial role in immunity against Brucella infection. Since the expression of IL-18 can be affected by polymorphisms in its gene, we decided to investigate any probable relationship between the six different IL-18 gene polymorphisms and brucellosis. A total of 193 patients with brucellosis and 83 healthy farmers who consumed contaminated raw milk and dairy products from the animals with brucellosis, were included in this study. All the individuals were genotyped for six IL-18 polymorphisms at positions -656, -607, -137, +113, +127 and codon 35/3, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The distributions of alleles for IL-18 polymorphisms at positions -137G/+113T/+127C/codon 35/3A (correlated with higher production of IL-18) were significantly higher in healthy controls than in patients (P=0.012, 0.012, 0.012 and 0.0018, respectively). It could be suggested that individuals who inherited the aforementioned genotypes/alleles are able to produce higher levels of IL-18 at the onset of infection, and it leads to more IFN-gamma production and control Brucella infection before the emerging brucellosis. 相似文献
964.
Olière S Douville R Sze A Belgnaoui SM Hiscott J 《Cytokine & growth factor reviews》2011,22(4):197-210
Infection with the Human T-cell Leukemia virus type I (HTLV-1) retrovirus results in a number of diverse pathologies, including the aggressive, fatal T-cell malignancy adult T-cell leukemia (ATL) and the chronic, progressive neurologic disorder termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Worldwide, it is estimated there are 15-20 million HTLV-1-infected individuals; although the majority of HTLV-1-infected individuals remain asymptomatic carriers (AC) during their lifetime, 2-5% of AC develops either ATL or HAM/TSP, but never both. Regardless of asymptomatic status or clinical outcome, HTLV-1 carriers are at high risk of opportunistic infection. The progression to pathological HTLV-1 disease is in part attributed to the failure of the innate and adaptive immune system to control virus spread. The innate immune response against retroviral infection requires recognition of viral pathogen-associated molecular patterns (PAMPs) through pattern-recognition receptors (PRR) dependent pathways, leading to the induction of host antiviral and inflammatory responses. Recent studies have begun to characterize the interplay between HTLV-1 infection and the innate immune response and have identified distinct gene expression profiles in patients with ATL or HAM/TSP--upregulation of growth regulatory pathways in ATL and constitutive activation of antiviral and inflammatory pathways in HAM/STP. In this review, we provide an overview of the replicative lifecycle of HTLV-1 and the distinct pathologies associated with HTLV-1 infection. We also explore the innate immune mechanisms that respond to HTLV-1 infection, the strategies used by HTLV-1 to subvert these defenses and their contribution to HTLV-1-associated diseases. 相似文献
965.
966.
Instrumental responses are hypothesized to be of two kinds: habitual and goal-directed, mediated by the sensorimotor and the associative cortico-basal ganglia circuits, respectively. The existence of the two heterogeneous associative learning mechanisms can be hypothesized to arise from the comparative advantages that they have at different stages of learning. In this paper, we assume that the goal-directed system is behaviourally flexible, but slow in choice selection. The habitual system, in contrast, is fast in responding, but inflexible in adapting its behavioural strategy to new conditions. Based on these assumptions and using the computational theory of reinforcement learning, we propose a normative model for arbitration between the two processes that makes an approximately optimal balance between search-time and accuracy in decision making. Behaviourally, the model can explain experimental evidence on behavioural sensitivity to outcome at the early stages of learning, but insensitivity at the later stages. It also explains that when two choices with equal incentive values are available concurrently, the behaviour remains outcome-sensitive, even after extensive training. Moreover, the model can explain choice reaction time variations during the course of learning, as well as the experimental observation that as the number of choices increases, the reaction time also increases. Neurobiologically, by assuming that phasic and tonic activities of midbrain dopamine neurons carry the reward prediction error and the average reward signals used by the model, respectively, the model predicts that whereas phasic dopamine indirectly affects behaviour through reinforcing stimulus-response associations, tonic dopamine can directly affect behaviour through manipulating the competition between the habitual and the goal-directed systems and thus, affect reaction time. 相似文献
967.
Kathleen A. Trychta Emily J. Heathward Agnieszka Sulima Susanne Bäck Mehdi Farokhnia Christopher T. Richie 《Biomarkers》2013,18(8):756-765
AbstractContext: Endoplasmic reticulum (ER) calcium depletion is associated with diverse diseases, including cardiac, hepatic, and neurologic diseases.Objective: The aim of the present study was to identify and characterize an endogenous protein that could be used to monitor ER calcium depletion comparably to a previously described exogenous reporter protein.Materials and methods: The use of a selective esterase-fluorescein diester pair allowed for carboxylesterase activity in extracellular fluid to be measured using a fluorescent readout. Cell culture media from three different cell lines, rat plasma, and human serum all possess quantifiable amounts of esterase activity.Results: Fluorescence produced by the interaction of carboxylesterases with a fluorescein diester substrate tracks with pharmacological and physiological inducers of ER calcium depletion. The fluorescence measured for in vitro and in vivo samples were consistent with ER calcium depletion being the trigger for increased esterase activity.Discussion: Decreased luminal ER calcium causes ER resident esterases to be released from the cell, and, when assessed concurrently with other disease biomarkers, these esterases may provide insight into the role of ER calcium homeostasis in human diseases.Conclusion: Our results indicate that carboxylesterases are putative markers of ER calcium dysfunction. 相似文献
968.
Mehdi Rajabi Elena Gorincioi Enzo Santaniello 《Nucleosides, nucleotides & nucleic acids》2013,32(6):474-481
Cytokinins and cytokinin nucleosides are purine derivatives with potential anticancer activity both in vitro and in vivo. N6-furfuryladenosine (kinetin riboside, KR) displays antiproliferative and apoptogenic activity against various human cancer cell lines and has recently been shown to suppress tumor growth in murine xenograft models of human leukemia and melanoma. In this study, we demonstrate that KR is able to inhibit the proliferation in HCT-15 human colon cancer cells in a dose-dependent manner with a concentration of 2.5 μM, which causes 50% inhibition of cell viability. The cell cycle analysis by flow cytometry showed that KR arrested cell cycle progression in the S Phase by blocking through G2/M and G0/G1 phase in HCT-15 colon cells. Moreover, suppression of clonogenic activity occurs after exposure to KR at a concentration of 2.5 μM for HCT-15. 相似文献
969.
Jean-Jacques Helesbeux Damien Peyronnet Mehdi Labaïed Philippe Grellier François Frappier Denis Seraphin 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):431-437
The synthesis of 1,2-dioxolane derivatives in two different acetophenone series, as simplified models of natural coumarins is described. 2-Acetyl-3-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl)phenyl acetate and 2-acetyl-5-acetoxy-4-(3-hydroperoxy-3-methylbut-1-enyl) phenyl acetate synthons are used as precursors to these structures. In vitro antimalarial activity of the 1,2-dioxolane derivatives has been investigated. 相似文献
970.
Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes 总被引:1,自引:0,他引:1
Constanze Buhrmann Parviz Shayan Bharat B Aggarwal Mehdi Shakibaei 《Arthritis research & therapy》2013,15(6):R202