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91.
Platelet aggregation activity due to platelet-activating factor (PAF) was detected at high molecular weight (HMW) and low molecular weight fractions after gel-filtration chromatography of cell lysate of endothelial cells. [3H]PAF added to the cell lysate was similarly distributed after chromatography. The radioactivity associated with HMW fraction was not reduced by digesting the lysate with trypsin, suggesting that PAF was not making complexes with proteins but was included in lipid vesicles in cell lysate. Further evidence showed that an unknown specific factor(s) was needed to form these PAF-containing lipid vesicles. Radioactivity was not found in HMW fraction when [3H]PAF was mixed with cell lysate of vascular smooth muscle cells. When monomeric PAF was added to endothelial cell lysate, the specific activity of aggregation decreased to the level exerted by endogenous PAF-containing lipid vesicles due to incorporation into lipid vesicles. PAF in the form of lipid vesicles was more stable in plasma than monomeric form. 相似文献
92.
Kim B. Saunders Patricia A. D’Amore 《In vitro cellular & developmental biology. Animal》1992,28(7-8):521-528
Summary Heterotypic cell-cell interactions appear to be involved in the control of development and function in a wide variety of tissues.
In the vasculature, endothelial cells and mural cells (smooth muscle cells or pericytes) make frequent contacts, suggesting
a role for intercellular interactions in the regulation of vascular growth and function. We have previously grown endothelial
cells and mural cells together in mixed cultures and found that heterocellular contact led to endothelial growth inhibition.
However, this mixed culture system does not lend itself to the examination of the effects of contact on the phenotype of the
individual cell types. We have therefore developed a co-culture system in which cells can be co-cultured across a porous membrane,
permitting intercellular contact while maintaining pure cell populations. Co-culture of endothelial cells and smooth muscle
cells across membranes with pore sizes of 0.02, 0.4, 0.6, and 0.8μm maintained the two cell types as homogeneous populations, whereas smooth muscle cells migrated across the membrane through
pores of 2.0μm. Vascular cell co-culture across membranes with 0.8-μm pores resulted the inhibition of endothelial cell proliferation and the generation of conditioned media which inhibited
endothelial cell growth. The arrangement of the cells in this co-culture system mimics thein vivo orientation of vascular cells in which mural cells are separated from the abluminal surface of the endothelium by a fenestrated
internal elastic lamina or basement membrane. Because this co-culture system maintains separable populations of cells in contact
or close proximity allowing for biochemical and molecular analyses of pure populations, it should prove useful for the study
of cell-cell interactions in a variety of systems. 相似文献
93.
Jan-Kan Chen Ying-Tung Lau Jackson Chu 《In vitro cellular & developmental biology. Animal》1992,28(2):143-145
Summary Rat aortic endothelial cells were found to exhibit clonal variations in response to EGF stimulation in cell growth and prostacyclin
synthesis. EGF-induced growth and prostacyclin synthesis appeared to be regulated in a coordinated manner in that a clone
with a higher response to EGF growth stimulation also exhibited a higher response to EGF-stimulated prostacyclin synthesis.
This observation implys a possible involvement of prostacyclin synthesis in some of the biological effects of EGF on vascular
endothelial cells. 相似文献
94.
Michel P. Rathbone Pamela J. Middlemiss John W. Gysbers Susan DeForge Penny Costello Rolando F. Del Maestro 《In vitro cellular & developmental biology. Animal》1992,28(7-8):529-536
Summary Presumptive astrocytes isolated from 10-day white Leghorn chick embryos, Factor VIII-positive human brain capillary endothelial
cells, meningeal fibroblasts from 10-day chick embryos, Swiss mouse 3T3 cells, and human astrocytoma cell lines, SKMG-1 and
U373, were rendered quiescent when placed in culture medium that contained 0 or 0.2% serum for 48 h; their proliferation was
markedly reduced and they incorporated [3H]thymidine at a low rate. [3H]Thymidine incorporation and cell proliferation were induced in all types of cells by addition of guanosine, GMP, GDP, GTP,
and to a lesser extent, adenosine, AMP, ADP or ATP to the culture medium. The stimulation of proliferation by adenosine and
guanosine was abolished by 1,3-dipropyl-7-methylxanthine (DPMX), an adenosine A2 receptor antagonist, but not by 1,3,-dipropyl-8-(2-amino-4-chorophenyl)xanthine (PACPX), an A1 antagonist. Stimulation of proliferation by the nucleotides was not abolished by either DPMX or PACPX. The P2 receptor agonists,α,β-methyleneATP and 2-methylthioATP, also stimulated [3H]thymidine incorporation into the cells with peak activity at approximately 3.5 and 0.03 nM, respectively. These data imply that adenosine and guanosine stimulate proliferation of these cell types through activation
of an adenosine A2 receptor, and the stimulation of cell proliferation by the nucleotides may be due to the activation of purinergic P2y receptors. As the primary cultures grew older their growth rate slowed. The capacity of the purine nucleosides and nucleotides
to stimulate their growth diminished concomitantly. The 3T3 cells showed neither decreased growth with increased passages
nor reduced response to the purines. In contrast, although the doubling time of the immortalized human astrocytoma cell lines
SKMG-1 and U373 remained constant, the responsiveness to purinergic stimulation of the U373 cells decreased but that of the
SKMG-1 did not. These data are compatible with a decrease in the number, or the ligand-binding affinity of the purinergic
receptors, or a decreased coupling of purinergic receptors to intracellular mediators in primary cells aged in tissue culture. 相似文献
95.
Robert L. Vender 《In vitro cellular & developmental biology. Animal》1992,28(6):403-409
Summary The development of pulmonary hypertension in a wide variety of human disease states and experimental animal models characterized
by chronic alveolar hypoxia is mediated by two pathologic vascular processes, a) vasoconstriction and b) vasoconstruction
(structural remodeling). The anatomic changes seen within the pulmonary circulation include a) increased deposition of collagen
and elastin in the adventitial layer and b) aberrant pulmonary vascular smooth muscle cell proliferation and maturation in
the medial segments. Despite the demonstrated ability of pharmacologic manipulation in the experimental animal to ameliorate
both the structural and hemodynamic changes, the actual etiologic mechanisms are only beginning to be explored. Using the
cell culture technique of co-cultivation, we have investigated the potential role of bovine pulmonary arterial endothelial
cell-derived factors in mediating abnormal bovine smooth muscle cell growth under conditions of reduced oxygen tension. We
have demonstrated that these cultured endothelial cells exposed in vitro to reduced levels of atmospheric oxygen concentrations
of 5.0% and 2.5% O2 for durations of 24 to 72 h produce and secrete soluble growth factor(s) which stimulate smooth muscle cell proliferation
when compared to cells maintained under standard tissue culture oxygen conditions of 95% room air. This growth-stimulatory
effect required the concomitant presence of serum factors (0.5% fetal bovine serum), was inhibited by heparin, was distinct
from platelet-derived growth factor, and seemed to have a molecular weight greater than 14 000 Da. We conclude that reduced
levels of oxygen tension in vitro can selectively induce pulmonary arterial endothelial cells to release mitogen(s) which
can stimulate vascular smooth muscle replication. Furthermore, we speculate that this in vitro finding may be of importance
as an etiologic mechanism to explain the accelerated smooth muscle cell growth characteristic of hypoxic pulmonary arteriopathy. 相似文献
96.
Studies on the lipid metabolism of the metacercariae of Clinostomum complanatum (Trematoda: Digenea)
Metacercariae of Clinostomum complanatum possess considerable amounts of lipids. Fractionation of the lipids shows triglycerides and phospholipids as the major components whereas cholesterol and free fatty acids are minor components. Furthermore phospholipid fractions by thin layer chromatography reveal lecithin and cephalin as the major polar lipids whereas lysolecithin and lysocephalin are present in small fractions. The specific activity of lipase (E.C. 3.1.1.3) is 150.8 μg free fatty acids liberated/mg protein/h. Epinephrine, testosterone, insulin, sodium fluoride and iodoacetate stimulated, but 2-propanol inhibited, the lipase activity. 相似文献
97.
H. Stam H. Jansen W.C. Hülsmann 《Biochemical and biophysical research communications》1980,96(2):899-906
Chylomicron degradation by hearts from fed and fasted rats was studied using a perfusion technique, which allows the separate collection of coronary (Qrv) and interstitial effluent (Qi). Upon perfusion with [3H]-cholesterol-containing chylomicrons the tissue recovery of label was highest in the fasted state, while label recovered in Qi was highest in the fed state. Density gradient centrifugation of Qi indicated that the label was recovered in lipoproteins with higher densities: low density lipoproteins (1.019<d<1.050), high density lipoproteins (1.050<d<1.21) and a fraction of d>1.21. These particles probably represent chylomicron degradation products (remnants and “surface fragments”). Our results indicate that tissue cholesterol uptake during chylomicron degradation may be inhibited in the fed state. Furthermore, the role of the myocyte (or interstitial) lipoprotein lipase in chylomicron degradation is discussed. 相似文献
98.
Repair of a vascular wound is mediated by migration and subsequent replication of the endothelial cells that form the inner lining of blood vessels. We have measured the growth response of human umbilical vein endothelial cells (HuE) to two polypeptides that are transiently produced in high concentrations at the site of a wound; the platelet-derived growth factor (PDGF) and the protease thrombin. When 104 HuE cells are seeded as a dense island (2-mm diameter) in the center of a 16-mm tissue culture well in medium containing 20% human serum derived from platelet-poor plasma (PDS), no increase in cell number or colony size is observed. With the addition of 0.5 ng/ml partially purified PDGF, colony size increases and the number of cells after 8 days is 4.8 × 104. When human thrombin (1 μg/ml) is added along with the PDGF, the cell number rises to 9.2 × 104. Thrombin alone stimulates no increase in cell number. Although partially purified PDGF stimulates endothelial cells maintained in PDS as well as those maintained in whole blood serum (WBS), pure PDGF is active only when assayed in medium that contains WBS and is supplemented with thrombin. These results suggest the existence of a second class of platelet-derived factors that enable HuE cells to respond to the mitogenic activity of the purified platelet mitogen and thrombin. 相似文献
99.
《Cell cycle (Georgetown, Tex.)》2013,12(12):2253-2259
Blocking tumor angiogenesis is an important goal of cancer therapy, but clinically approved anti-angiogenic agents suffer from limited efficacy and adverse side effects, fueling the need to identify alternative angiogenesis regulators. Tumor endothelial marker 8 (TEM8) is a highly conserved cell surface receptor overexpressed on human tumor vasculature. Genetic disruption of Tem8 in mice revealed that TEM8 is important for promoting tumor angiogenesis and tumor growth but dispensable for normal development and wound healing. The induction of TEM8 in cultured endothelial cells by nutrient or growth factor deprivation suggests that TEM8 may be part of a survival response pathway that is activated by tumor microenvironmental stress. In preclinical studies, antibodies targeted against the extracellular domain of TEM8 inhibited tumor angiogenesis and blocked the growth of multiple human tumor xenografts. Anti-TEM8 antibodies augmented the activity of other anti-angiogenic agents, vascular targeting agents and conventional chemotherapeutic agents and displayed no detectable toxicity. Thus, anti-TEM8 antibodies provide a promising new tool for selective blockade of neovascularization associated with cancer and possibly other angiogenesis-dependent diseases. 相似文献
100.
Pancreatic lipase (PL), a key enzyme responsible for the hydrolysis of triacylglycerides in the gastrointestinal tract, has been identified as the therapeutic target for the regulation of lipid absorption. In the present study, six major constituents from a famous Chinese herbal medicine Cortex Mori Radicis (also named sangbaipi in Chinese), have been collected and their inhibitory effects on PL have been carefully investigated and well characterized by a fluorescence-based assay. The results clearly demonstrated that all tested bioactive constituents from Cortex Mori Radicis including sanggenone C (SC), sanggenone D (SD), kuwanon C (KC), kuwanon G (KG), morin and morusin displayed strong to moderate inhibitory effects towards PL with the IC50 values ranging from 0.77 μM to 20.56 μM. Further investigations on inhibition kinetics demonstrated that SC, SD, KC and KG functioned as potent and mixed inhibitors against PL-mediated 4-MU oleate hydrolysis, with the Ki values less than 5.0 μM. Furthermore, molecular docking simulations demonstrated that SD (the most potent PL inhibitor from Cortex Mori Radicis) could create strong interaction with Ser152 (the key amino acid in the catalytic triad) of PL via hydrogen bonding. All these findings provided a new powerful evidence for explaining the hypolipidemic effect of Cortex Mori Radicis, also suggested that some abundant natural compounds in this herbal medicine could be served as lead compounds for the development of new PL inhibitors. 相似文献