全文获取类型
收费全文 | 3444篇 |
免费 | 298篇 |
国内免费 | 3篇 |
专业分类
3745篇 |
出版年
2021年 | 29篇 |
2020年 | 22篇 |
2019年 | 33篇 |
2018年 | 39篇 |
2017年 | 43篇 |
2016年 | 51篇 |
2015年 | 96篇 |
2014年 | 99篇 |
2013年 | 123篇 |
2012年 | 182篇 |
2011年 | 155篇 |
2010年 | 118篇 |
2009年 | 96篇 |
2008年 | 142篇 |
2007年 | 166篇 |
2006年 | 181篇 |
2005年 | 134篇 |
2004年 | 142篇 |
2003年 | 119篇 |
2002年 | 137篇 |
2001年 | 73篇 |
2000年 | 52篇 |
1999年 | 52篇 |
1998年 | 54篇 |
1997年 | 38篇 |
1996年 | 44篇 |
1995年 | 34篇 |
1994年 | 37篇 |
1993年 | 40篇 |
1992年 | 46篇 |
1991年 | 54篇 |
1990年 | 37篇 |
1989年 | 43篇 |
1988年 | 35篇 |
1987年 | 42篇 |
1986年 | 32篇 |
1985年 | 22篇 |
1984年 | 33篇 |
1983年 | 30篇 |
1982年 | 27篇 |
1981年 | 23篇 |
1979年 | 29篇 |
1977年 | 23篇 |
1976年 | 28篇 |
1975年 | 28篇 |
1973年 | 20篇 |
1972年 | 22篇 |
1971年 | 21篇 |
1970年 | 21篇 |
1968年 | 23篇 |
排序方式: 共有3745条查询结果,搜索用时 15 毫秒
101.
102.
The intracellular compartmentation of Ap4A in various growth and cell-cycle stages in mammalian cells was studied by applying a non-aqueous extraction procedure for cell nuclei. In both slowly and in exponentially growing Ehrlich ascites tumour cells from random cultures, more than 75% of the whole cellular Ap4A content is localized in the nuclei. In G1 and early S-phase cells of synchronized baby hamster kidney (BHK) fibroblast cultures, approx. 90% of the intracellular Ap4A pool is confined to the nuclear compartment. In contrast, Ap4A is distributed to nearly equal amounts between cytoplasm and nuclei during mid-S phase. After transition through the S-phase, increasing proportions of Ap4A (78% 18 h and 96% 22 h after serum replenishing, respectively) are again localized in the nuclear compartment. 相似文献
103.
Roland Benz Michael D. Jones Farhan Younas Elke Maier Niraj Modi Reinhard Mentele Friedrich Lottspeich Ulrich Kleinekath?fer John Smit 《PloS one》2015,10(11)
Caulobacter crescentus is an oligotrophic bacterium that lives in dilute organic environments such as soil and freshwater. This bacterium represents an interesting model for cellular differentiation and regulation because daughter cells after division have different forms: one is motile while the other is non-motile and can adhere to surfaces. Interestingly, the known genome of C. crescentus does not contain genes predicted to code for outer membrane porins of the OmpF/C general diffusion type present in enteric bacteria or those coding for specific porins selective for classes of substrates. Instead, genes coding for 67 TonB-dependent outer membrane receptors have been identified, suggesting that active transport of specific nutrients may be the norm. Here, we report that high channel-forming activity was observed with crude outer membrane extracts of C. crescentus in lipid bilayer experiments, indicating that the outer membrane of C. crescentus contained an ion-permeable channel with a single-channel conductance of about 120 pS in 1M KCl. The channel-forming protein with an apparent molecular mass of about 20 kDa was purified to homogeneity. Partial protein sequencing of the protein indicated it was a member of the OmpW family of outer membrane proteins from Gram-negative bacteria. This channel was not observed in reconstitution experiments with crude outer membrane extracts of an OmpW deficient C. crescentus mutant. Biophysical analysis of the C. crescentus OmpW suggested that it has features that are special for general diffusion porins of Gram-negative outer membranes because it was not a wide aqueous channel. Furthermore, OmpW of C. crescentus seems to be different to known OmpW porins and has a preference for ions, in particular cations. A putative model for OmpW of C. crescentus was built on the basis of the known 3D-structures of OmpW of Escherichia coli and OprG of Pseudomonas aeruginosa using homology modeling. A comparison of the two known structures with the model of OmpW of C. crescentus suggested that it has a more hydrophilic interior and possibly a larger diameter. 相似文献
104.
In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination 总被引:1,自引:0,他引:1 下载免费PDF全文
R Armstrong V L Friedrich K V Holmes M Dubois-Dalcq 《The Journal of cell biology》1990,111(3):1183-1195
A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with [3H]thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease. 相似文献
105.
106.
Jochen Schulze Sebastian Seitz Hiroaki Saito Michael Schneebauer Robert P. Marshall Anke Baranowsky Bjoern Busse Arndt F. Schilling Felix W. Friedrich Joachim Albers Alexander S. Spiro Jozef Zustin Thomas Streichert Kristina Ellwanger Christof Niehrs Michael Amling Roland Baron Thorsten Schinke 《PloS one》2010,5(4)
Wnt signalling is a key pathway controlling bone formation in mice and humans. One of the regulators of this pathway is Dkk1, which antagonizes Wnt signalling through the formation of a ternary complex with the transmembrane receptors Krm1/2 and Lrp5/6, thereby blocking the induction of Wnt signalling by the latter ones. Here we show that Kremen-2 (Krm2) is predominantly expressed in bone, and that its osteoblast-specific over-expression in transgenic mice (Col1a1-Krm2) results in severe osteoporosis. Histomorphometric analysis revealed that osteoblast maturation and bone formation are disturbed in Col1a1-Krm2 mice, whereas bone resorption is increased. In line with these findings, primary osteoblasts derived from Col1a1-Krm2 mice display a cell-autonomous differentiation defect, impaired canonical Wnt signalling and decreased production of the osteoclast inhibitory factor Opg. To determine whether the observed effects of Krm2 on bone remodeling are physiologically relevant, we analyzed the skeletal phenotype of 24 weeks old Krm2-deficient mice and observed high bone mass caused by a more than three-fold increase in bone formation. Taken together, these data identify Krm2 as a regulator of bone remodeling and raise the possibility that antagonizing KRM2 might prove beneficial in patients with bone loss disorders. 相似文献
107.
O. Friedrich S.J. Reiling J. Wunderlich P. Rohrbach 《Journal of cellular and molecular medicine》2014,18(9):1851-1862
Mutations in the multidrug resistance transporter of Plasmodium falciparum PfMDR1 have been implicated to play a significant role in the emergence of worldwide drug resistance, yet the molecular and biochemical mechanisms of this transporter are not well understood. Although it is generally accepted that drug resistance in P. falciparum is partly associated with PfMDR1 transport activity situated in the membrane of the digestive vacuole, direct estimates of the pump rate of this transport process in the natural environment of the intact host–parasite system have never been analysed. The fluorochrome Fluo‐4 is a well‐documented surrogate substrate of PfMDR1 and has been found to accumulate by actively being transported into the digestive vacuole of several parasitic strains. In the present study, we designed an approach to use Fluo‐4 fluorescence uptake as a measure of compartmental Fluo‐4 concentration accumulation in the different compartments of the host–parasite system. We performed a ‘reverse Fluo‐4 imaging' approach to relate fluorescence intensity to changes in dye concentration rather than Ca2+ fluctuations and were able to calculate the overall rate of transport for PfMDR1 in Dd2 parasites. With this assay, we provide a powerful method to selectively measure the effect of PfMDR1 mutations on substrate transport kinetics. This will be of high significance for future compound screening to test for new drugs in resistant P. falciparum strains. 相似文献
108.
109.
Heinz-Werner Hagedorn Rüdiger Schulz Anita Friedrich 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1992,577(2)
The metabolic transformation of methandienone (I) in the horse was investigated. After administration of a commercial drug preparation to a female horse (0.5 mg/kg), urine samples were collected up to 96 h and processed without enzymic hydrolysis. Extraction was performed by a series of solid—liquid and liquid—liquid extractions, thus avoiding laborious purification techniques. For analysis by gas chromatography—mass spectrometry, the extracts were trimethylsilylated. Besides the parent compound I and its C-17 epimer II, three monohydroxylated metabolites were identified: 6β-hydroxymethandienone (III), its C-17 epimer (IV) and 16β-hydroxy-methandienone (V). In addition, three isomers of 6β,16-dihydroxymethandienone (VIa–c) were discovered. Apparently, reduction of the δ4 double bond of 16β-hyroxymethandienone (V) in the horse yields 16β,17β-dihydroxy-17α-methyl-5β-androst-1-en-3-one (VII). Reduction of the isomers VIa–c results in the corresponding 6β,16,17-trihydroxy-17-methyl-5β-androst-1-en-3-ones (VIIIa–c). The data presented here suggest that screening for the isomers of VI and VIII, applying the selected-ion monitoring technique, will be the most successful way of proving methandienone administration to a horse. 相似文献
110.
Reduced paucimannosidic N‐glycan formation by suppression of a specific β‐hexosaminidase from Nicotiana benthamiana 下载免费PDF全文