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Claudia Brehm Sabine Huenecke Ruth Esser Stephan Kloess Andrea Quaiser Sibille Betz Olga Zimmermann Jan Soerensen Jakob R. Passweg Thomas Klingebiel Dirk Schwabe Peter Bader Ulrike Koehl 《Cancer immunology, immunotherapy : CII》2014,63(8):821-833
In a clinical phase I/II trial, pediatric patients with high-risk malignancies were treated with ex vivo IL-2-stimulated donor natural killer (NK) cells after transplantation with haploidentical stem cells. To evaluate the potential negative effects of the immunosuppressive drug mycophenolate mofetil (MMF) used for immunotherapy, the functionality and signaling of ex vivo NK cells was investigated. Our results show that during NK cell expansion, long-term (9 days) incubation with mycophenolic acid (MPA), the active metabolite of MMF, in therapeutically relevant concentrations led to the severe inhibition of NK cell proliferation. This correlated with a significantly reduced cytokine/chemokine secretion and the inhibited acquisition of surface receptors regarding cytotoxicity (e.g., NKp30, NKp44, NKp46, NKG2D), adhesion/migration (e.g., ICAM-1/CD54, LFA-1/CD11a, CD62L, CXCR3) and activation (e.g., CD25). Moreover, MPA prevented phosphorylation of the central signaling molecules STAT-3/-4/-5, AKT and ERK1/2. In contrast, short-term (24 h) MPA incubation of IL-2-stimulated NK cells had no or only marginal effects on the activated NK cell phenotype, including receptor expression, cytokine/chemokine secretion and intracellular signaling. Further, short-term MPA incubation only moderately affected the highly cytotoxic activity of previously IL-2-stimulated NK cells. In conclusion, while long-term MPA incubation significantly compromised ex vivo NK cell functionality, previously IL-2-activated NK cells seemed to be rather resistant to short-term MPA treatment. This finding supports the use of IL-2-activated NK cells as immunotherapy, especially for patients treated with MMF after haploidentical stem cell transplantation. 相似文献
94.
Esser D Kouril T Zaparty M Sierocinski P Chan PP Lowe T Van der Oost J Albers SV Schomburg D Makarova KS Siebers B 《Extremophiles : life under extreme conditions》2011,15(6):711-712
The thermoacidophiles Sulfolobus solfataricus P2 and S. acidocaldarius 98-3 are considered key model organisms representing a major phylum of the Crenarchaeota. Because maintaining current, accurate genome information is indispensable for modern biology, we have updated gene function annotation using the arCOGs database, plus other available functional, structural and phylogenetic information. The goal of this initiative is continuous improvement of genome annotation with the support of the Sulfolobus research community. 相似文献
95.
This longitudinal study from Germany examined the dynamic progression of antisocial behavior in childhood and adolescence based on the social interactional model by Patterson, DeBaryshe, and Ramsey. It examined the link between antisocial behavior, social rejection, academic failure, and affiliation with deviant peers in a sample of 1,657 children and youths aged between 6 and 15 years who were studied at three measurement waves (T1 to T3) over a time period of about 5 years. Teachers rated the children on all variables, parents additionally provided ratings of antisocial behavior and social rejection. Latent structural equation modeling yielded the predicted positive paths from antisocial behavior at T1 to social rejection and academic failure at T2. As predicted, affiliation with deviant peers at T2 was positively associated with social rejection and academic failure at the same measurement point. Finally, affiliation with deviant peers at T2 significantly predicted antisocial behavior at T3. 相似文献
96.
Summary Wild-type strains of Aspergillus niger were transformed with integrative vectors. The number of stable transformants varied from approximately 20–30/g up to 17,000/g using acetamide and hygromycin B selection, respectively. The introduction of deletions of 5 and 3 non-coding regions of the acetamidase gene (amdS+) revealed that these sequences influenced the number of transformants. The molecular characterization of A. niger transformants revealed that several copies of the vectors were tandemly integrated into the nuclear DNA. These oligomers were stably inherited, even after 100 days of growth on non-selective medium. The expression of the vector-encoded genes was confirmed by evidence from the mRNAs and corresponding proteins encoded by the selectable marker genes.
Offprint requests to: K. Esser 相似文献
97.
Rabbit Cells Expressing Human CD4 and Human CCR5 Are Highly Permissive for Human Immunodeficiency Virus Type 1 Infection 总被引:2,自引:2,他引:2 下载免费PDF全文
Roberto F. Speck Michael L. Penn Jrg Wimmer Ursula Esser Bishop F. Hague Thomas J. Kindt Robert E. Atchison Mark A. Goldsmith 《Journal of virology》1998,72(7):5728-5734
To evaluate the feasibility of using transgenic rabbits expressing CCR5 and CD4 as a small-animal model of human immunodeficiency virus type 1 (HIV) disease, we examined whether the expression of the human chemokine receptor (CCR5) and human CD4 would render a rabbit cell line (SIRC) permissive to HIV replication. Histologically, SIRC cells expressing CD4 and CCR5 formed multinucleated cells (syncytia) upon exposure to BaL, a macrophagetropic strain of HIV that uses CCR5 for cell entry. Intracellular viral capsid p24 staining showed abundant viral gene expression in BaL-infected SIRC cells expressing CD4 and CCR5. In contrast, neither SIRC cells expressing CD4 alone nor murine 3T3 cells expressing CCR5 and CD4 exhibited significant expression of p24. These stably transfected rabbit cells were also highly permissive for the production of virions upon infection by two other CCR5-dependent strains (JR-CSF and YU-2) but not by a CXCR4-dependent strain (NL4-3). The functional integrity of these virions was demonstrated by the successful infection of human peripheral blood mononuclear cells (PBMC) with viral stocks prepared from these transfected rabbit cells. Furthermore, primary rabbit PBMC were found to be permissive for production of infectious virions after circumventing the cellular entry step. These results suggest that a transgenic rabbit model for the study of HIV disease may be feasible. 相似文献
98.
The physical state of membrane lipids modulates the activation of the first component of complement.
A F Esser R M Bartholomew J W Parce H M McConnell 《The Journal of biological chemistry》1979,254(6):1768-1770
Activation of the first component of human complement (C1) by bilayer-embedded nitroxide spin label lipid haptens and specific rabbit antinitroxide antibody has been measured. The nitroxide spin label hapten was contained in host bilayers of either dimyristoyl phosphatidylcholine or dipalmitoyl phosphatidylcholine in the form of both liposomes and vesicles. At a temperature of 32 degrees C, which is intermediate between the hydrocarbon chain-melting temperatures of the two phospholipids, activation of C1 in such vesicles and liposomes is more efficient in the fluid membrane. Studies of C1 activation in binary mixtures of cholesterol and dipalmitoyl phosphatidylcholine indicate that the activation of C1 is not limited by the lateral diffusion of the lipid haptens in these membranes. 相似文献
99.
Thielens NM Enrie K Lacroix M Jaquinod M Hernandez JF Esser AF Arlaud GJ 《The Journal of biological chemistry》1999,274(14):9149-9159
The Ca2+-dependent interaction between complement serine proteases C1r and C1s is mediated by their alpha regions, encompassing the major part of their N-terminal CUB-EGF-CUB (where EGF is epidermal growth factor) module array. In order to define the boundaries of the C1r domain(s) responsible for Ca2+ binding and Ca2+-dependent interaction with C1s and to assess the contribution of individual modules to these functions, the CUB, EGF, and CUB-EGF fragments were expressed in eucaryotic systems or synthesized chemically. Gel filtration studies, as well as measurements of intrinsic Tyr fluorescence, provided evidence that the CUB-EGF pair adopts a more compact conformation in the presence of Ca2+. Ca2+-dependent interaction of intact C1r with C1s was studied using surface plasmon resonance spectroscopy, yielding KD values of 10.9-29.7 nM. The C1r CUB-EGF pair bound immobilized C1s with a higher KD (1.5-1.8 microM), which decreased to 31.4 nM when CUB-EGF was used as the immobilized ligand and C1s was free. Half-maximal binding was obtained at comparable Ca2+ concentrations ranging from 5 microM with intact C1r to 10-16 microM for C1ralpha and CUB-EGF. The isolated CUB and EGF fragments or a CUB + EGF mixture did not bind C1s. These data demonstrate that the C1r CUB-EGF module pair (residues 1-175) is the minimal segment required for high affinity Ca2+ binding and Ca2+-dependent interaction with C1s and indicate that Ca2+ binding induces a more compact folding of the CUB-EGF pair. 相似文献
100.