全文获取类型
收费全文 | 966篇 |
免费 | 49篇 |
国内免费 | 39篇 |
出版年
2023年 | 14篇 |
2022年 | 22篇 |
2021年 | 26篇 |
2020年 | 40篇 |
2019年 | 40篇 |
2018年 | 36篇 |
2017年 | 22篇 |
2016年 | 27篇 |
2015年 | 28篇 |
2014年 | 59篇 |
2013年 | 76篇 |
2012年 | 51篇 |
2011年 | 69篇 |
2010年 | 42篇 |
2009年 | 48篇 |
2008年 | 56篇 |
2007年 | 51篇 |
2006年 | 58篇 |
2005年 | 47篇 |
2004年 | 43篇 |
2003年 | 27篇 |
2002年 | 23篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 16篇 |
1998年 | 5篇 |
1997年 | 12篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 11篇 |
1983年 | 9篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1973年 | 2篇 |
排序方式: 共有1054条查询结果,搜索用时 15 毫秒
151.
Mutations in the genes that encode Connexin 26 (GJB2) and Connexin 30 (GJB6) are the most common known cause of hereditary nonsyndromic sensorineural deafness. Cx26 and Cx30 share a similar protein structure, as well as the same expression distribution pattern in the cochlea. Cx26 has different intracellular trafficking properties compared to those of Cx43 and Cx32, whose trafficking manner is consistent with the classical membrane protein secretory pathway. Until now, however, the trafficking patterns of Cx30 have not been studied. By means of an immunofluorescence staining approach, we found that the targeting of Cx30 to gap junctions in transfected HeLa cells is not affected by brefeldin A, suggesting a Golgi-independent feature, similar to Cx26. Nocodazole had a minimal effect on assembly and distribution of Cx30 gap junctions. Cytochalasin B-induced actin filament depolymerization, however, affected both the pattern and the distribution of Cx30 gap junctions. Co-localization with and/or interaction between Cx30 and microtubules and cortical actin filaments, but not with the tight/adherens junction protein ZO-1, was confirmed by immunofluorescence and/or immunoprecipitation methods. The results suggest that the cytoskeleton, and especially actin filaments, are important components in the processes of assembly, trafficking and stabilization of Cx30 gap junctions. 相似文献
152.
153.
A graph-theoretic method for the basic reproduction number in continuous time epidemiological models
Tomás de-Camino-Beck Mark A. Lewis P. van den Driessche 《Journal of mathematical biology》2009,59(4):503-516
In epidemiological models of infectious diseases the basic reproduction number is used as a threshold parameter to determine the threshold between disease extinction and outbreak. A graph-theoretic form
of Gaussian elimination using digraph reduction is derived and an algorithm given for calculating the basic reproduction number
in continuous time epidemiological models. Examples illustrate how this method can be applied to compartmental models of infectious
diseases modelled by a system of ordinary differential equations. We also show with these examples how lower bounds for can be obtained from the digraphs in the reduction process. 相似文献
154.
Cláudio Maia Cecília Santos Fernando Schmitt Silvia Socorro 《Journal of cellular biochemistry》2009,107(4):667-676
Regucalcin plays an important role in maintenance of intracellular Ca2+ homeostasis, suppresses cell proliferation, inhibits expression of oncogenes, and increases the expression of tumour suppressor genes. This suggests that regucalcin functions may be altered in cancer tissues. In this study the regucalcin expression in breast and prostate cancer cases was analysed by RT‐PCR and immunohistochemistry showing that the mRNA and/or protein are under‐expressed in these tumors. The effect of sex steroid hormones on regucalcin expression in breast and prostate cancer cells was determined by real‐time PCR. MCF‐7 and LNCaP cells were stimulated with 0, 1, and 10 nM of 17β‐estradiol (E2) or 5α‐dihydrotestosterone (DHT), respectively, for 0, 6, 12, 24, and 48 h. MCF‐7 cells were also stimulated with E2 conjugated to BSA (E2‐BSA). To explore the mechanisms underlying the sex steroid regulation of regucalcin expression, control treatments with ICI 182,780, flutamide and cyclohexamide were carried out. E2 effects regulating regucalcin expression were not abrogated in the presence of ICI 182,780, and were similar to those observed with E2‐BSA, which suggests the involvement of a membrane‐bound estrogen receptor. In LNCaP cells, DHT down‐regulated regucalcin expression, an effect inhibited by the presence of both flutamide and cyclohexamide, suggesting the involvement of androgen receptor and de novo protein synthesis. The loss of regucalcin expression in breast and prostate cancer cases and the regulation of its expression by sex steroid hormones suggest that it may be associated with development and progression of these human tumors. J. Cell. Biochem. 107: 667–676, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
155.
We describe several gender structured population models governed by logistic growth with non-linear death rate. We extend these models to include groups of people isolated from sexual activity and individuals exposed to a mild and long-lasting sexually transmitted disease, i.e. without disease-induced mortality and recovery. The transmission of the disease is modeled through formation/separation of heterosexual couples assuming that one infected individual automatically infects his/her partner. We are interested in how the non-reproductive class may change the demographic tendencies in the general population and whether they can curb the growth of the infected group while keeping the healthy one at acceptable levels. A comparison of the equilibrium total population size in the presence and the absence of the isolated class is also provided. 相似文献
156.
Akinori Kashio Akiko Amano Takashi Sakamoto Mitsuya Suzuki Tatsuya Yamasoba 《Biochemical and biophysical research communications》2009,390(3):394-2294
Using senescence marker protein 30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize vitamin C (VC), we examined whether modulating VC level affects age-related hearing loss (AHL). KO and wild-type (WT) C57BL/6 mice were given water containing 1.5 g/L VC [VC(+)] or 37.5 mg/L VC [VC(−)]. At 10 months of age, KO VC(−) mice showed significant reduction in VC level in the inner ear, plasma, and liver, increase in auditory brainstem response (ABR) thresholds, and decrease in the number of spiral ganglion cells compared to WT VC(−), WT VC(+), and KO VC(+) mice. There were no differences in VC level in the inner ear, ABR thresholds, or the number of spiral ganglion cells among WT VC(−), WT VC(+), and KO VC(+) mice. These findings suggest that VC depletion can accelerate AHL but that supplementing VC may not increase VC level in the inner ear or slow AHL in mice. 相似文献
157.
Keith T. Gagnon Xinxin Zhang Guosheng Qu Shyamasri Biswas Jimmy Suryadi Bernard A. Brown II E. Stuart Maxwell 《RNA (New York, N.Y.)》2010,16(1):79-90
The archaeal L7Ae and eukaryotic 15.5kD protein homologs are members of the L7Ae/15.5kD protein family that characteristically recognize K-turn motifs found in both archaeal and eukaryotic RNAs. In Archaea, the L7Ae protein uniquely binds the K-loop motif found in box C/D and H/ACA sRNAs, whereas the eukaryotic 15.5kD homolog is unable to recognize this variant K-turn RNA. Comparative sequence and structural analyses, coupled with amino acid replacement experiments, have demonstrated that five amino acids enable the archaeal L7Ae core protein to recognize and bind the K-loop motif. These signature residues are highly conserved in the archaeal L7Ae and eukaryotic 15.5kD homologs, but differ between the two domains of life. Interestingly, loss of K-loop binding by archaeal L7Ae does not disrupt C′/D′ RNP formation or RNA-guided nucleotide modification. L7Ae is still incorporated into the C′/D′ RNP despite its inability to bind the K-loop, thus indicating the importance of protein–protein interactions for RNP assembly and function. Finally, these five signature amino acids are distinct for each of the L7Ae/L30 family members, suggesting an evolutionary continuum of these RNA-binding proteins for recognition of the various K-turn motifs contained in their cognate RNAs. 相似文献
158.
Cátia Sousa Madalena Ribeiro Ana Teresa Rufino Alcino Jorge Leitão 《Journal of receptor and signal transduction research》2017,37(2):181-188
Context/objective: Cell lines used to study the role of the G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor (GPER) as a mediator of estrogen responses have yielded conflicting results. This work identified a simple assay to predict cell line competence for pharmacological studies of GPR30.Materials and methods: The phosphorylation or expression levels of ERK1/2, Akt, c-Fos and eNOS were evaluated to assess GPR30 activation in response to known agonists (17β-estradiol and G-1) in MCF-7 and T-47D breast cancer cell lines and in bovine aortic endothelial cells. GPR30 expression was analyzed by qRT-PCR and Western blot with two distinct antibodies directed at its carboxy and amino terminals.Results: None of the agonists, at any of the concentrations tested, activated any of those target proteins. Additional experiments excluded the disruption of the signaling pathway, interference of phenol red in the culture medium and constitutive proteasome degradation of GPR30 as possible causes for the lack of response of the three cell lines. Analysis of receptor expression showed the absence of clearly detectable GPR30 species of 44 and 50–55?kDa previously identified in cell lines that respond to 17β-estradiol and G-1.Discussion and conclusion: Cells that do not express the 44 and 50–55?kDa species do not respond to GPR30 agonists. Thus, the presence or absence of these GPR30 species is a simple and rapid manner to determine whether a given cell line is suitable for pharmacological or molecular studies of GPR30 modulation. 相似文献
159.
160.