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71.
In variable environments, it is probable that environmental conditions in the past can influence demographic performance now. Cohort effects occur when these delayed life-history effects are synchronized among groups of individuals in a population. Here we show how plasticity in density-dependent demographic traits throughout the life cycle can lead to cohort effects and that there can be substantial population dynamic consequences of these effects. We show experimentally that density and food conditions early in development can influence subsequent juvenile life-history traits. We also show that conditions early in development can interact with conditions at maturity to shape future adult performance. In fact, conditions such as food availability and density at maturity, like conditions early in development, can generate cohort effects in mature stages. Based on these data, and on current theory about the effects of plasticity generated by historical environments, we make predictions about the consequences of such changes on density-dependent demography and on mite population dynamics. We use a stochastic cohort effects model to generate a range of population dynamics. In accordance with the theory, we find the predicted changes in the strength of density dependence and associated changes in population dynamics and population variability. 相似文献
72.
Lan R Geng H Polichnowski AJ Singha PK Saikumar P McEwen DG Griffin KA Koesters R Weinberg JM Bidani AK Kriz W Venkatachalam MA 《American journal of physiology. Renal physiology》2012,302(9):F1210-F1223
We investigated the signaling basis for tubule pathology during fibrosis after renal injury. Numerous signaling pathways are activated physiologically to direct tubule regeneration after acute kidney injury (AKI) but several persist pathologically after repair. Among these, transforming growth factor (TGF)-β is particularly important because it controls epithelial differentiation and profibrotic cytokine production. We found that increased TGF-β signaling after AKI is accompanied by PTEN loss from proximal tubules (PT). With time, subpopulations of regenerating PT with persistent loss of PTEN (phosphate and tension homolog) failed to differentiate, became growth arrested, expressed vimentin, displayed profibrotic JNK activation, and produced PDGF-B. These tubules were surrounded by fibrosis. In contrast, PTEN recovery was associated with epithelial differentiation, normal tubule repair, and less fibrosis. This beneficial outcome was promoted by TGF-β antagonism. Tubule-specific induction of TGF-β led to PTEN loss, JNK activation, and fibrosis even without prior AKI. In PT culture, high TGF-β depleted PTEN, inhibited differentiation, and activated JNK. Conversely, TGF-β antagonism increased PTEN, promoted differentiation, and decreased JNK activity. Cre-Lox PTEN deletion suppressed differentiation, induced growth arrest, and activated JNK. The low-PTEN state with JNK signaling and fibrosis was ameliorated by contralateral nephrectomy done 2 wk after unilateral ischemia, suggesting reversibility of the low-PTEN dysfunctional tubule phenotype. Vimentin-expressing tubules with low-PTEN and JNK activation were associated with fibrosis also after tubule-selective AKI, and with human chronic kidney diseases of diverse etiology. By preventing tubule differentiation, the low-PTEN state may provide a platform for signals initiated physiologically to persist pathologically and cause fibrosis after injury. 相似文献
73.
Mertz Christoffer Krarup Sara Jensen Cecilie D. Lindholm Sandy E. H. Kjær Christina Pinborg Lars H. Bak Lasse K. 《Neurochemical research》2020,45(6):1247-1255
Neurochemical Research - Epilepsy is one of the most common chronic neurological conditions. Today, close to 30 different medications to prevent epileptic seizures are in use; yet, far from all... 相似文献
74.
Isolation of nuclei from label-retaining cells and measurement of their turnover rates in rat colon 总被引:3,自引:0,他引:3
Kim SJ Cheung S Hellerstein MK 《American journal of physiology. Cell physiology》2004,286(6):C1464-C1473
We describe here a new technique for isolating nuclei from long-term label-retaining cells (LRCs), a subpopulation enriched with stem cells from colon, and for measuring their proliferation rates in vivo. A double-label approach was developed, combining the use of bromodeoxyuridine (BrdU) and 2H2O. Male Fisher 344 rats were administered BrdU in drinking water continuously for 28 wk. BrdU was then discontinued (BrdU washout), and animals (n = 33) were switched to 2H2O in drinking water and killed after 2, 4, and 8 wk. Nuclei from BrdU-positive cells (LRCs) were collected by flow cytometry. The percentages of LRCs were 7 and 3.8% after 4 and 8 wk of BrdU washout, respectively. Turnover rates of LRCs were measured on the basis of deuterium incorporation from 2H2O into DNA of LRC nuclei, as determined by mass spectrometry. The proliferation rate of the LRCs collected was 0.330.90% per day (half-life of 77210 days). Significant contamination from other potentially long-lived colon cells was excluded. In conclusion, this double-labeling method allows both physical isolation of nuclei from colon epithelial LRCs and measurement of their in vivo proliferation rates. Use of this approach may allow better understanding of mechanisms by which agents induce or protect against colon carcinogenesis. carcinogenesis; deuterated water; long-term label-retaining cells; stable isotopes 相似文献
75.
76.
Lindenbaum M Perkins E Csonka E Fleming E Garcia L Greene A Gung L Hadlaczky G Lee E Leung J MacDonald N Maxwell A Mills K Monteith D Perez CF Shellard J Stewart S Stodola T Vandenborre D Vanderbyl S Ledebur HC 《Nucleic acids research》2004,32(21):e172
Mammalian artificial chromosomes (MACs) provide a means to introduce large payloads of genetic information into the cell in an autonomously replicating, non-integrating format. Unique among MACs, the mammalian satellite DNA-based Artificial Chromosome Expression (ACE) can be reproducibly generated de novo in cell lines of different species and readily purified from the host cells' chromosomes. Purified mammalian ACEs can then be re-introduced into a variety of recipient cell lines where they have been stably maintained for extended periods in the absence of selective pressure. In order to extend the utility of ACEs, we have established the ACE System, a versatile and flexible platform for the reliable engineering of ACEs. The ACE System includes a Platform ACE, containing >50 recombination acceptor sites, that can carry single or multiple copies of genes of interest using specially designed targeting vectors (ATV) and a site-specific integrase (ACE Integrase). Using this approach, specific loading of one or two gene targets has been achieved in LMTK− and CHO cells. The use of the ACE System for biological engineering of eukaryotic cells, including mammalian cells, with applications in biopharmaceutical production, transgenesis and gene-based cell therapy is discussed. 相似文献
77.
78.
Palmitoylation of the Autographa californica multicapsid nucleopolyhedrovirus envelope glycoprotein GP64: mapping,functional studies,and lipid rafts 下载免费PDF全文
Budded virions (BV) of the baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) contain a major envelope glycoprotein known as GP64, which was previously shown to be palmitoylated. In the present study, we used truncation and amino acid substitution mutations to map the palmitoylation site to cysteine residue 503. Palmitoylation of GP64 was not detected when Cys503 was replaced with alanine or serine. Palmitoylation-minus forms of GP64 were used to replace wild-type GP64 in AcMNPV, and these viruses were used to examine potential functions of GP64 palmitoylation in the context of the infection cycle. Analysis by immunoprecipitation and cell surface studies revealed that palmitoylation of GP64 did not affect GP64 synthesis or its transport to the cell surface in Sf9 cells. GP64 proteins lacking palmitoylation also mediated low-pH-triggered membrane fusion in a manner indistinguishable from that of wild-type GP64. Cells infected with viruses expressing palmitoylation-minus forms of GP64 produced infectious virions at levels similar to those from cells infected with wild-type AcMNPV. In combination, these data suggest that virus entry and exit in Sf9 cells were not significantly affected by GP64 palmitoylation. To determine whether GP64 palmitoylation affected the association of GP64 with membrane microdomains, the potential association of GP64 with lipid raft microdomains was examined. These experiments showed that: (i) AcMNPV-infected Sf9 cell membranes contain lipid raft microdomains, (ii) GP64 association with lipid rafts was not detected in infected Sf9 cells, and (iii) GP64 palmitoylation did not affect the apparent exclusion of GP64 from lipid raft microdomains. 相似文献
79.
Brown NL Knott L Halligan E Yarram SJ Mansell JP Sandy JR 《Development, growth & differentiation》2003,45(2):153-165
The mammalian face is assembled in utero in a series of complex and interdependent molecular, cell and tissue processes. The orofacial complex appears to be exquisitely sensitive to genetic and environmental influence and this explains why clefts of the lip and palate are the most common congenital anomaly in humans (one in 700 live births). In this study, microarray technology was used to identify genes that may play pivotal roles in normal murine palatogenesis. mRNA was isolated from murine embryonic palatal shelves oriented vertically (before elevation), horizontally (following elevation, before contact), and following fusion. Changes in gene expression between the three different stages were analyzed with GeneChip microarrays. A number of genes were upregulated or downregulated, and large changes were seen in the expression of loricrin, glutamate decarboxylase, gamma-amino butyric acid type A receptor beta3 subunit, frizzled, Wnt-5a, metallothionein, annexin VIII, LIM proteins, Sox1, plakophilin1, cathepsin K and creatine kinase. In this paper, the changes in genetic profile of the developing murine palate are presented, and the possible role individual genes/proteins may play during normal palate development are discussed. Candidate genes with a putative role in cleft palate are also highlighted. 相似文献
80.
Li W Nugent MA Zhao Y Chau AN Li SJ Chou IN Liu G Kagan HM 《Journal of cellular biochemistry》2003,88(1):152-164
Lysyl oxidase (LO) plays a central role in the crosslinking of collagen and elastin in the extracellular matrix. Here we demonstrate that basic fibroblast growth factor (bFGF), a polypeptide which regulates proliferation, differentiation, and migration of a variety of cell types, is a substrate of LO. The oxidation of lysine residues in bFGF by LO resulted in the covalent crosslinking of bFGF monomers to form dimers and higher order oligomers and dramatically altered its biological properties. Both the mitogenic potential and the nuclear localization of bFGF were markedly inhibited in the Swiss 3T3 cells upon its oxidation by LO. NIH 3T3 IgBNM 6-1 cells (6-1 cells) overexpress bFGF which participates in an autocrine mechanism accounting for the transformation of these cells into a tumorigenic state. Exposure of the 6-1 cells to nanomolar concentrations of LO in culture oxidized lysine and generated crosslinkages in bFGF within the cell and markedly reduced proliferative rates. The lack of LO expression has been correlated with hyperproliferative cell growth, while this enzyme has been identified as a suppressor of ras-induced tumorigenesis. The present results illustrate a mechanism by which LO can depress normal and transformed cell growth. 相似文献