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排序方式: 共有865条查询结果,搜索用时 15 毫秒
61.
Lingor P Teusch N Schwarz K Mueller R Mack H Bähr M Mueller BK 《Journal of neurochemistry》2007,103(1):181-189
Inhibitory molecules derived from CNS myelin and glial scar tissue are major causes for insufficient functional regeneration in the mammalian CNS. A multitude of these molecules signal through the Rho/Rho kinase (ROCK) pathway. We evaluated three inhibitors of ROCK, Y- 27632, Fasudil (HA-1077), and Dimethylfasudil (H-1152), in models of neurite outgrowth in vitro. We show, that all three ROCK inhibitors partially restore neurite outgrowth of Ntera-2 neurons on the inhibitory chondroitin sulphate proteoglycan substrate. In the rat optic nerve crush model Y-27632 dose-dependently increased regeneration of retinal ganglion cell axons in vivo. Application of Dimethylfasudil showed a trend towards increased axonal regeneration in an intermediate concentration. We demonstrate that inhibition of ROCK can be an effective therapeutic approach to increase regeneration of CNS neurons. The selection of a suitable inhibitor with a broad therapeutic window, however, is crucial in order to minimize unwanted side effects and to avoid deleterious effects on nerve fiber growth. 相似文献
62.
Leonhartsberger N Ramoner R Putz T Gander H Rahm A Falkensammer C Bartsch G Thurnher M 《Cancer immunology, immunotherapy : CII》2007,56(6):897-903
The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously
been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore
other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal
cell carcinoma patients.
In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83+ monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated
with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover,
proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced
after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation
was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion.
Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with
a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components
and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and
that monocytes may limit DC vaccination induced immunity.
Supported by a grant to Martin Thurnher from the kompetenzzentrum medizin tirol (kmt), a center of excellence. 相似文献
63.
Putz T Ramoner R Gander H Rahm A Bartsch G Bernardo K Ramsay S Thurnher M 《Cancer immunology, immunotherapy : CII》2007,56(5):627-640
Bee venom secretory phospholipase A2 (bv-sPLA2) and phosphatidylinositol-(3,4)-bisphosphate (PtdIns(3,4)P2) act synergistically
to induce cell death in tumour cells of various origins with concomitant stimulation of the immune system. Here, we investigated
the mechanisms involved in such actions and examined structural requirements of PtdIns-homologues to inhibit tumour cells
in combination with bv-sPLA2. Renal cancer cells were treated with bv-sPLA2 alone or in combination with PtdIns-homologues.
Inhibitory effects on [3H] thymidine incorporation and intracellular signal transduction pathways were tested. Reaction products generated by bv-sPLA2
interaction with PtdIns(3,4)P2 were identified by mass spectrometry. Among the tested PtdIns-homologues those with a phosphate
esterified to position 3 of the inositol head group, were most efficient in cooperating with bv-sPLA2 to block tumour cell
proliferation. Growth inhibition induced by the combined action of bv-sPLA2 with either PtdIns(3,4)bisphosphate or PtdIns(3,4,5)trisphosphate
were synergistic and accompanied by potent cell lysis. In contrast, PtdIns, which lacked the phosphate group at position 3,
failed to promote synergistic growth inhibition. The combined administration of PtdIns(3,4)P2 and bv-sPLA2 abrogated signal
transduction mediated by extracellular signal regulated kinase 1 and 2 and prevented transduction of survival signals mediated
by protein kinase B. Surface expression of the epidermal growth factor (EGF)-receptor was reduced after PtdIns(3,4)P2-bv-sPLA2
administration and associated with a blockade of EGF-induced signalling. In addition, mass spectroscopy revealed that bv-sPLA2
cleaves PtdIns(3,4)P2 to generate lyso-PtdIns(3,4)P2. In conclusion, we suggest that the cytotoxic activity mediated by PtdIns(3,4)P2
and bv-sPLA2 is due to cell death that results from disruption of membrane integrity, abrogation of signal transduction and
the generation of cytotoxic lyso-PtdIns(3,4)P2.
This work was supported by a grant to MT of the kompetenzzentrum medizin tirol (kmt), a centre of excellence. 相似文献
64.
Wang Y Beck W Deppisch R Marshall SM Hoenich NA Thompson MG 《American journal of physiology. Cell physiology》2007,293(1):C328-C336
Advanced glycation end products (AGE) are substantially elevated in individuals with diabetes and/or chronic kidney disease (CKD). These patients are at greatly increased risk of cardiovascular events. The purpose of this study was to investigate the novel hypothesis that AGE elicit externalization of the platelet membrane phospholipid phosphatidylserine (PS). This contributes to hemostasis through propagation of the coagulation cascade leading to thrombus formation. Platelet-rich plasma (PRP) was prepared by differential centrifugation, and PS externalization was quantified by a fluorescence-activated cell sorter using annexin V-FITC. Human serum albumin (HSA)-AGE was generated by incubating HSA with glucose for 2, 4, or 6 wk, and total HSA-AGE was assessed by fluorescence intensity. The 2-wk HSA-AGE preparation (02 mg/ml) stimulated a concentration-dependent increase in PS externalization in a subpopulation of platelets that was threefold at 2 mg/ml. In contrast, the 4- and 6-wk preparations were maximal at 0.5 mg/ml and fivefold in magnitude. These effects mirrored the change in total HSA-AGE content of the preparations. The PS response was maximal at 10 min and inhibited by the PKC- inhibitor rottlerin and the serotonin [5-hydroxytryptamine (5-HT)]2A/2C receptor antagonist ritanserin in a dose-dependent manner. Moreover, the 5-HT2A/2C receptor agonist 1,2,5-dimethoxy-4-iodophenyl-2-aminopropane mimicked the effect of HSA-AGE on PS externalization. These data demonstrate, for the first time, that HSA-AGE stimulates PS externalization in a subpopulation of platelets via the 5-HT2A/2C receptor. This may have important consequences for platelet involvement in inflammatory responses and the increased cardiovascular risk observed in individuals with diabetes and/or CKD. signal transduction; thrombosis; caspase-3 相似文献
65.
Since direct benefits are likely to be absent in the grasshopper Chorthippus biguttulus, indirect genetic benefits are a potential explanation for costly female preference. Choosy females may improve their fitness in terms of enhanced attractiveness of sons alone or additionally by improved viability of offspring. We tested the predictions of these two hypotheses by comparing attractiveness-related song traits and viability in offspring of attractive and unattractive grasshopper males. The experiment was conducted with larvae reared under semi natural lab conditions in one year and under natural conditions in the field in the following year. If reared under natural conditions no significant differences in viability and song traits between offspring of attractive and unattractive males could be found. Offspring reared in the lab produced calling songs with a significantly more exact song rhythm when sired by attractive males than offspring of unattractive males. Offspring of attractive males should thus have a theoretical advantage in mate choice, which, however, did not translate into higher attractiveness values in acoustic female choice experiments. Therefore our experiments could not resolve whether female choice in C. biguttulus evolved according to the sexy son hypothesis. Since viability in offspring of attractive males did not differ from offspring of unattractive males, “good genes” seems unlikely to be the underlying mechanism of female choice. 相似文献
66.
Kathrin I Odörfer Nina J Unger Karin Weber Eric P Sandgren Reinhold G Erben 《BMC biotechnology》2007,7(1):30
Background
Immune-mediated rejection of labeled cells is a general problem in transplantation studies using cells labeled with any immunogenic marker, and also in gene therapy protocols. The aim of this study was to establish a syngeneic model for long-term histological cell tracking in the absence of immune-mediated rejection of labeled cells in immunocompetent animals. We used inbred transgenic Fischer 344 rats expressing human placental alkaline phosphatase (hPLAP) under the control of the ubiquitous R26 promoter for this study. hPLAP is an excellent marker enzyme, providing superb histological detection quality in paraffin and plastic sections. 相似文献67.
68.
Wagner D Hanwell HE Schnabl K Yazdanpanah M Kimball S Fu L Sidhom G Rousseau D Cole DE Vieth R 《The Journal of steroid biochemistry and molecular biology》2011,126(3-5):72-77
24,25-Dihydroxyvitamin D (24,25VD) is a major catabolite of 25-hydroxyvitamin D (25VD) metabolism, and may be physiologically active. Our objectives were to: (1) characterize the response of serum 24,25VD(3) to vitamin D(3) (VD(3)) supplementation; (2) test the hypothesis that a higher 24,25VD(3) to 25VD(3) ratio (24,25:25VD(3)) predicts 25VD(3) response. Serum samples (n=160) from wk 2 and wk 6 of a placebo-controlled, randomized clinical trial of VD(3) (28,000IU/wk) were analyzed for serum 24,25VD(3) and 25VD(3) by mass spectrometry. Serum 24,25VD(3) was highly correlated with 25VD(3) in placebo- and VD(3)-treated subjects at each time point (p<0.0001). At wk 2, the 24,25:25VD(3) ratio was lower with VD(3) than with placebo (p=0.035). From wk 2 to wk 6, the 24,25:25VD(3) ratio increased with the VD(3) supplement (p<0.001) but not with placebo, such that at wk 6 this ratio did not significantly differ between groups. After correcting for potential confounders, we found that 24,25:25VD(3) at wk 2 was inversely correlated to the 25VD(3) increment by wk 6 in the supplemented group (r=-0.32, p=0.02) but not the controls. There is a strong correlation between 24,25VD(3) and 25VD(3) that is only modestly affected by VD(3) supplementation. This indicates that the catabolism of 25VD(3) to 24,25VD(3) rises with increasing 25VD(3). Furthermore, the initial ratio of serum 24,25VD(3) to 25VD(3) predicted the increase in 25VD(3). The 24,25:25VD(3) ratio may therefore have clinical utility as a marker for VD(3) catabolism and a predictor of serum 25VD(3) response to VD(3) supplementation. 相似文献
69.
Understanding the molecular basis of how new species arise is a central question and prime challenge in evolutionary biology and includes understanding how genomes diversify. Eukaryotic cells possess an integrated compartmentalized genetic system of endosymbiotic ancestry. The cellular subgenomes in nucleus, mitochondria and plastids communicate in a complex way and co-evolve. The application of hybrid and cybrid technologies, most notably those involving interspecific exchanges of plastid and nuclear genomes, has uncovered a multitude of species-specific nucleo-organelle interactions. Such interactions can result in plastome-genome incompatibilities, which can phenotypically often be recognized as hybrid bleaching, hybrid variegation or disturbance of the sexual phase. The plastid genome, because of its relatively low number of genes, can serve as a valuable tool to investigate the origin of these incompatibilities. In this article, we review progress on understanding how plastome-genome co-evolution contributes to speciation. We genetically classify incompatible phenotypes into four categories. We also summarize genetic, physiological and environmental influence and other possible selection forces acting on plastid-nuclear co-evolution and compare taxa providing molecular access to the underlying loci. It appears that plastome-genome incompatibility can establish hybridization barriers, comparable to the Dobzhansky-Muller model of speciation processes. Evidence suggests that the plastid-mediated hybridization barriers associated with hybrid bleaching primarily arise through modification of components in regulatory networks, rather than of complex, multisubunit structures themselves that are frequent targets. 相似文献
70.
Marion Mayerhofer Reinhold Mayerhofer Deborah Topinka Jed Christianson Allen G Good 《BMC plant biology》2011,11(1):47