全文获取类型
收费全文 | 1250篇 |
免费 | 80篇 |
专业分类
1330篇 |
出版年
2023年 | 8篇 |
2022年 | 19篇 |
2021年 | 22篇 |
2020年 | 25篇 |
2019年 | 24篇 |
2018年 | 25篇 |
2017年 | 25篇 |
2016年 | 39篇 |
2015年 | 56篇 |
2014年 | 69篇 |
2013年 | 86篇 |
2012年 | 112篇 |
2011年 | 113篇 |
2010年 | 83篇 |
2009年 | 54篇 |
2008年 | 81篇 |
2007年 | 68篇 |
2006年 | 70篇 |
2005年 | 71篇 |
2004年 | 54篇 |
2003年 | 45篇 |
2002年 | 54篇 |
2001年 | 16篇 |
2000年 | 7篇 |
1999年 | 11篇 |
1998年 | 9篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1976年 | 2篇 |
1973年 | 2篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1969年 | 7篇 |
1965年 | 1篇 |
1960年 | 2篇 |
1959年 | 2篇 |
1958年 | 1篇 |
1956年 | 1篇 |
排序方式: 共有1330条查询结果,搜索用时 15 毫秒
1.
Vital staining of mitochondria with a fluorescent dye 3,3′-diethyloxacarbocyanine was used to follow cell lineage in embryos of Phallusia mammillata. The results agree in general with the plan established by Conklin in 1905. Strong fluorescence migrated after fertilization similarly to the pigment of the “yellow crescent” in Styela. Later, fluorescence segregated into muscle cell primordia, but not into mesenchyme cells. An animal hemisphere cell, b 8.17 also exhibited strong fluorescence and joined a group of muscle primordia, very likely becoming a muscle cell itself. In the tadpole, all the tail muscle cells were fluorescent. Fluorescence was also noticed in nerve cell primordia of the vegetal hemisphere, particularly in the cell A 8.16 whose descendants appeared to become part of the sensory vesicle which was strongly fluorescent in the tadpole. The usefulness of this type of vital staining in following cell lineage of colorless embryos is stressed. 相似文献
2.
3.
4.
Differential Regulation and Function of CD73, a Glycosyl-Phosphatidylinositol–linked 70-kD Adhesion Molecule, on Lymphocytes and Endothelial Cells 下载免费PDF全文
Laura Airas Jussi Niemel Marko Salmi Tarja Puurunen David J. Smith Sirpa Jalkanen 《The Journal of cell biology》1997,136(2):421-431
CD73, otherwise known as ecto-5′-nucleotidase, is a glycosyl-phosphatidylinositol–linked 70-kD molecule expressed on different cell types, including vascular endothelial cells (EC) and certain subtypes of lymphocytes. There is strong evidence for lymphocyte CD73 having a role in several immunological phenomena such as lymphocyte activation, proliferation, and adhesion to endothelium, but the physiological role of CD73 in other cell types is less clear. To compare the biological characteristics of CD73 in different cell types, we have studied the structure, function, and surface modulation of CD73 on lymphocytes and EC. CD73 molecules on lymphocytes are shed from the cell surface as a consequence of triggering with an antiCD73 mAb, mimicking ligand binding. In contrast, triggering of endothelial CD73 does not have any effect on its expression. Lymphocyte CD73 is susceptible to phosphatidylinositol phospholipase, whereas only a small portion of CD73 on EC could be removed by this enzyme. Furthermore, CD73 on EC was unable to deliver a tyrosine phosphorylation inducing signal upon mAb triggering, whereas triggering of lymphocyte CD73 can induce tyrosine phosphorylation. Despite the functional differences, CD73 molecules on lymphocytes and EC were practically identical structurally, when studied at the protein, mRNA, and cDNA level. Thus, CD73 is an interesting example of a molecule which lacks structural variants but yet has a wide diversity of biological functions. We suggest that the ligand- induced shedding of lymphocyte CD73 represents an important and novel means of controlling lymphocyte– EC interactions. 相似文献
5.
Cardiac mitochondrial ATP-sensitive potassium channel is activated by nitric oxide in vitro 总被引:1,自引:0,他引:1
Previous observations on the activation of the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) by nitric oxide (NO) in myocardial preconditioning were based on indirect evidence. In this study, we have investigated the direct effect of NO on the rat cardiac mitoK(ATP) after reconstitution of the inner mitochondrial membranes into lipid bilayers. We found that the mitoK(ATP) was activated by exogenous NO donor S-nitroso-N-acetyl penicillamine or PAPA NONOate. This activation was inhibited by mitoK(ATP) blockers 5-hydroxydecanoate or glibenclamide. Our observations confirm that NO can directly activate the cardiac mitoK(ATP), which may underlie its contribution to myocardial preconditioning. 相似文献
6.
Mammalian p55CDC Mediates Association of the Spindle Checkpoint Protein Mad2 with the Cyclosome/Anaphase-promoting Complex, and is Involved in Regulating Anaphase Onset and Late Mitotic Events 总被引:20,自引:0,他引:20 下载免费PDF全文
Marko Kallio Jasminder Weinstein John R. Daum Daniel J. Burke Gary J. Gorbsky 《The Journal of cell biology》1998,141(6):1393-1406
We have investigated the function of p55CDC, a mammalian protein related to Cdc20 and Hct1/Cdh1 in Saccharomyces cerevisiae, and Fizzy and Fizzy-related in Drosophila. Immunofluorescence studies and expression of a p55CDC-GFP chimera demonstrate that p55CDC is concentrated at the kinetochores in M phase cells from late prophase to telophase. Some p55CDC is also associated with the spindle microtubules and spindle poles, and some is diffuse in the cytoplasm. At anaphase, the concentration of p55CDC at the kinetochores gradually diminishes, and is gone by late telophase. In extracts prepared from M phase, but not from interphase HeLa cells, p55CDC coimmunoprecipitates with three important elements of the M phase checkpoint machinery: Cdc27, Cdc16, and Mad2. p55CDC is required for binding Mad2 with the Cdc27 and Cdc16. Thus, it is likely that p55CDC mediates the association of Mad2 with the cyclosome/anaphase-promoting complex. Microinjection of anti-p55CDC antibody into mitotic mammalian cells induces arrest or delay at metaphase, and impairs progression of late mitotic events. These studies suggest that mammalian p55CDC may be part of a regulatory and targeting complex for the anaphase-promoting complex. 相似文献
7.
Martin Pilhofer Marko PavlekovicNatuschka M. Lee Wolfgang LudwigKarl-Heinz Schleifer 《Systematic and applied microbiology》2009
Few reports on in situ mRNA detection in bacteria have been published, even though a major aim in environmental microbiology is to link function/activity to the identity of the organisms. This study reports a reliable approach for the in situ detection of nifH mRNA using fluorescence hybridization based on a previously described protocol for pmoA. nifH codes for a dinitrogenase reductase, a key enzyme in dinitrogen fixation. nifH mRNA was hybridized with a digoxigenin-labelled polynucleotide probe. The hybrid was detected with an anti-DIG-antibody labelled with horseradish peroxidase. Subsequently, the signal was amplified by catalyzed reporter deposition (CARD) with fluorochrome-labelled tyramides. Furthermore, the imaged organisms were identified using standard fluorescence in situ hybridization of rRNA. Thus, the approach enabled us specifically to link in situ the information from the dinitrogen fixation activity of an organism to its identity. Unexpectedly, the signals derived from nifH mRNA hybridization showed a distinct uneven pattern within the cells. This indicated that the method used could even give insights about the localization of the detected mRNA within the cell, which is a potential use of mRNA fluorescence in situ hybridization (FISH) that has not been reported up to now for bacterial cells. 相似文献
8.
Background
Cysteine cathepsins are normally found in the lysosomes where they are involved in intracellular protein turnover. Their ability to degrade the components of the extracellular matrix in vitro was first reported more than 25 years ago. However, cathepsins were for a long time not considered to be among the major players in ECM degradation in vivo. During the last decade it has, however, become evident that abundant secretion of cysteine cathepsins into extracellular milieu is accompanying numerous physiological and disease conditions, enabling the cathepsins to degrade extracellular proteins.Scope of view
In this review we will focus on cysteine cathepsins and their extracellular functions linked with ECM degradation, including regulation of their activity, which is often enhanced by acidification of the extracellular microenvironment, such as found in the bone resorption lacunae or tumor microenvironment. We will further discuss the ECM substrates of cathepsins with a focus on collagen and elastin, including the importance of that for pathologies. Finally, we will overview the current status of cathepsin inhibitors in clinical development for treatment of ECM-linked diseases, in particular osteoporosis.Major conclusions
Cysteine cathepsins are among the major proteases involved in ECM remodeling, and their role is not limited to degradation only. Deregulation of their activity is linked with numerous ECM-linked diseases and they are now validated targets in a number of them. Cathepsins S and K are the most attractive targets, especially cathepsin K as a major therapeutic target for osteoporosis with drugs targeting it in advanced clinical trials.General significance
Due to their major role in ECM remodeling cysteine cathepsins have emerged as an important group of therapeutic targets for a number of ECM-related diseases, including, osteoporosis, cancer and cardiovascular diseases. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. 相似文献9.
Ahlqvist KJ Hämäläinen RH Yatsuga S Uutela M Terzioglu M Götz A Forsström S Salven P Angers-Loustau A Kopra OH Tyynismaa H Larsson NG Wartiovaara K Prolla T Trifunovic A Suomalainen A 《Cell metabolism》2012,15(1):100-109
Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations. 相似文献
10.
1. We describe a generalized mainland-island metapopulation model which includes migration among the island populations. We test model predictions with quantitative data on more than 200 species of moths in two contrasting networks of small islands. The data include a direct measure of migration rate, based on trapping of moths on rocky skerries with no local populations of the vast majority of species.
2. We predicted that moths which are strong fliers but uncommon on the islands have a higher incidence on scattered islands than on islands in a group, because the latter 'compete' for immigrants from the mainland. In contrast, we predicted that weakly flying species with potentially large local populations on the islands occur more frequently on islands in a group due to enhanced colonization rate.
3. Both predicted patterns were observed. Island occupancy increased significantly with the number of individuals caught on the rocky skerries, which is our measure of migration rate from the mainland, supporting the basic assumption that the species occur on the islands in a balance between colonizations and extinctions.
4. These results demonstrate that the moth metapopulations on islands represent a mixture of Levins's and mainland-island metapopulations, and that the mixture is different for different species in the same landscape. 相似文献
2. We predicted that moths which are strong fliers but uncommon on the islands have a higher incidence on scattered islands than on islands in a group, because the latter 'compete' for immigrants from the mainland. In contrast, we predicted that weakly flying species with potentially large local populations on the islands occur more frequently on islands in a group due to enhanced colonization rate.
3. Both predicted patterns were observed. Island occupancy increased significantly with the number of individuals caught on the rocky skerries, which is our measure of migration rate from the mainland, supporting the basic assumption that the species occur on the islands in a balance between colonizations and extinctions.
4. These results demonstrate that the moth metapopulations on islands represent a mixture of Levins's and mainland-island metapopulations, and that the mixture is different for different species in the same landscape. 相似文献