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1.
Inhibition of retroviral mRNA expression in the murine macrophage cell line GG2EE by biologic response modifiers 总被引:4,自引:0,他引:4
We immortalized the GG2EE macrophage (M phi) cell line by infection of freshly isolated bone marrow cells with the recombinant J2 retrovirus carrying v-raf and v-myc oncogenes. We investigated the expression of J2 virus mRNA in relationship with the proliferative ability and tumoricidal activity of GG2EE cells exposed to biologic response modifiers (BRM). Calcium ionophore (Ca2+I), picolinic acid (PA), or IFN-gamma were employed to activate GG2EE cells. Each BRM was due to inhibit the proliferation of GG2EE cells in a dose-dependent manner, whereas only Ca2+I or the combined treatment with PA plus IFN-gamma induced tumoricidal GG2EE cells. J2 virus mRNA expression was not affected by PA or IFN-gamma, but it was dramatically decreased by Ca2+I or PA plus IFN-gamma. These results indicated that the expression of J2 mRNA can be inhibited in GG2EE cells by appropriate BRM such as Ca2+I or IFN-gamma plus PA. In contrast, the expression of 2'5'-oligoadenylate synthetase mRNA was augmented to similar levels by treatment of the GG2EE cells with IFN-gamma alone or in combination with PA. The down-regulation of J2 mRNA expression was not associated with the antiproliferative activity of the BRM but rather with their ability to induce tumoricidal activity. These results suggest that the process of activation of tumoricidal macrophages also triggers a mechanism(s) of resistance to viral mRNA expression. Moreover, the finding that IFN-gamma or PA inhibit cell proliferation but not J2 mRNA expression indicates that the intracellular targets of these BRM are intact, independent from and unaffected by J2 virus expression. 相似文献
2.
A Riccio C B Bruni M Rosenberg M Gottesman K McKenney F Blasi 《Journal of bacteriology》1985,163(3):1172-1179
3.
The receptor for urokinase-plasminogen activator 总被引:8,自引:0,他引:8
Many human cells and cell lines possess a specific receptor that binds urokinase plasminogen activator (uPA) with an affinity of about 10(-10) M. Bound enzyme is not internalized, is slowly dissociated, and retains its enzymatic activity. The amino acid sequence of uPA responsible for receptor binding is located within the first 35 aminoterminal residues, ie, in the growth factor domain. Binding, however, is not competed for by other proteins that contain the growth factor domain (including epidermal growth factor). Cells that produce uPA secrete the pro-uPA form, which subsequently binds to the receptor. A431 cells, in fact, have their receptors completely saturated with pro-uPA. It is proposed that uPA:uPA-receptor interaction plays a direct role in physiological and pathological processes that require cell migration. 相似文献
4.
5.
L Varesio M Clayton E Blasi R Ruffman D Radzioch 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(12):4265-4271
We have studied the effects of picolinic acid, a product of tryptophan degradation, on the activation of mouse peritoneal macrophages (M phi). Picolinic acid acts synergistically with IFN-gamma in activating M phi from C57BL/6 mice. Moreover, M phi from C3H/HeJ mice and C3H/HeN that do not become cytotoxic in response to IFN-gamma alone could be fully activated by exposure to picolinate plus IFN-gamma. These results indicate that picolinic acid is a potent costimulator of M phi activation that functions as a second signal. Inasmuch as we have previously demonstrated that the activation of cytotoxic M phi correlates with specific changes in ribosomal RNA (rRNA), we investigated whether picolinic acid could modify M phi RNA metabolism. Picolinic acid inhibited the synthesis of total M phi RNA, the accumulation of newly synthesized 28S rRNA, and augmented the steady state levels of rRNA precursors (pre-rRNA). These changes in RNA metabolism were similar to those previously described in murine M phi activated in vitro or in vivo to express tumoricidal activity. These results demonstrate that picolinic acid is a potent, biologic M phi second signal, suggest that the changes in rRNA are causally connected with the expression of tumoricidal activity, and suggest the existance of an autocrine effect mediated by picolinic acid. 相似文献
6.
Receptor-mediated internalization and degradation of urokinase is caused by its specific inhibitor PAI-1. 总被引:35,自引:2,他引:33 下载免费PDF全文
The receptor for urokinase plasminogen activator (uPA) has been previously shown not to internalize its ligand, but rather to focalize its activity at the cell surface, allowing a regulated cell surface plasmin dependent proteolysis. The receptor in fact binds the proenzyme pro-uPA and allows its very efficient conversion to the active two chains form. Receptor bound active uPA can also interact with its specific type 1 inhibiror (PAI-1) which is therefore able to inhibit the cell surface plasmin formation. In this paper we show that the uPA-PAI-1 complex bound to the uPA receptor is internalized and degraded. U937 cells were incubated at 4 degrees C with labeled uPA-PAI-1 (and other ligands), the temperature then raised to 37 degrees C and the fate of the ligand followed for 3 h thereafter. The uPA-PAI-1 complex was internalized into the cells (i.e. could not be dissociated by acid treatment) and thereafter degraded (i.e. appeared in the supernatant in a non TCA-precipitable form). Other ligands (free uPA, ATF and DFP-treated uPA) were not internalized nor degraded. The degradation of the uPA-PAI-1 complex is preceded by internalization and is inhibited by chloroquine, an inhibitor of lysosomal protein degradation. These data suggest the existence of a cellular cycle of uPA. After synthesis pro-uPA is secreted, bound to the receptor and activated to two chain uPA. On the surface, uPA can activate surface bound plasminogen to produce surface bound plasmin. In the presence of PAI-1 uPA activity is inhibited and plasmin production interrupted, while the uPA-PAI-1 complex is internalized and degraded. 相似文献
7.
Lucia Pitzurra Manuela Puliti Mohamed Ali Burhan Fuad Francesco Bistoni Elisabetta Blasi 《FEMS immunology and medical microbiology》1993,7(4):289-295
Abstract The present study was designed to establish the susceptibility of macrophage-mediated effector functions to tetanus toxin (TT). Using the murine macrophage cell line, GG2EE, generated in vitro by v- raf /v- myc oncogenes, we have previously provided evidence that TT selectively inhibits interferon gamma (IFN-γ), but not basal, lysozyme activity. Here we show that while neither phagocytic nor candidacidal activities are affected by TT treatment, antitumoral activity is significantly impaired after exposure to TT. This phenomenon, which is dose-dependent, is fully ascribed to the holotoxin, as heat inactivated TT, C or A-B fragments result ineffective. Furthermore, C but not A-B fragment competes with TT in abrogating its inhibitory effects. Overall, these data indicate that TT is not a broad-spectrum, down-regulating signal on macrophage-mediated functions, thus implying that its toxic action is exerted on specific molecular targets. 相似文献
8.
9.
A soluble, ligand binding mutant of the human urokinase plasminogen activator receptor. 总被引:6,自引:0,他引:6
A truncated version of the human urokinase plasminogen activator receptor has been obtained by in vitro mutagenesis by insertion of a premature nonsense codon in the urokinase plasminogen activator receptor cDNA. This results in a protein truncated immediately upstream of the region which appears to be required for membrane attachment of the receptor via a glycolipid anchor. The modified receptor cDNA inserted into an expression vector has been transfected into mouse LB6 cells. Transfectants produce a urokinase plasminogen activator (u-PA)-binding protein that is secreted into the medium. It can be cross-linked to iodinated ATF (amino-terminal fragment of u-PA) and can also inhibit binding of iodinated ATF to mouse LB6 cells that express the wild type human receptor. The soluble u-PA receptor will be used in a variety of experiments aimed at identifying the role and mechanism of u-PA in physiological and pathological invasive processes, as well as in therapeutical attempts to block or decrease cancer cell invasion and in general u-PA-mediated tissue destruction. 相似文献
10.
In vivo paracrine interaction between urokinase and its receptor: effect on tumor cell invasion 总被引:14,自引:0,他引:14 下载免费PDF全文
Numerous studies have linked the production of increased levels of urokinase type plasminogen activator (uPA) with the malignant phenotype. It has also been shown that a specific cell surface receptor can bind uPA through a domain distinct and distant from the proteolytic domain. In an in vivo model of invasion, consisting of experimentally modified chorioallantoic membrane (CAM) of a chick embryo, only cells that concurrently expressed both uPA and a receptor for uPA, and in which the receptor was saturated with uPA, were efficient in invasion. To test whether uPA produced by one cell can, in a paracrine fashion, affect the invasive capacity of a receptor-expressing cell, we transfected LB6 mouse cells with human uPA (LB6[uPA]), or human uPA-receptor cDNA (LB6[uPAR]). LB6(uPA) cells released into the medium 1-2 Ploug units of human uPA per 10(6) cells in 24 h. The LB6(uPAR) cells expressed on their surface approximately 12,000 high affinity (Kd 1.7 x 10(-10) M uPA binding sites per cell. Unlabeled LB6(uPA) and 125-IUdR-labeled LB6(uPAR) cells were coinoculated onto experimentally wounded and resealed CAMs and their invasion was compared to that of homologous mixtures of labeled and unlabeled LB6(uPAR) or LB6(uPA) cells. Concurrent presence of both cell types in the CAMs resulted in a 1.8-fold increase of invasion of the uPA-receptor expressing cells. A four-fold stimulation of invasion was observed when cells were cocultured in vitro, prior to in vivo inoculation. Enhancement of invasion was prevented in both sets of experiments by treatment with specific antihuman uPA antibodies, indicating that uPA was the main mediator of the invasion-enhancing, paracrine effect on the receptor-expressing cells. 相似文献