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91.
Erika Reus-Chavarría Ivette Martínez-Vieyra Cristina Salinas-Nolasco Araceli Evangelina Chávez-Piña Juan Vicente Méndez-Méndez Edgar Oliver López-Villegas Alejandro Sosa-Peinado Doris Cerecedo 《生物化学与生物物理学报:生物膜》2019,1861(2):387-402
Hypertension (HTN), i.e. abnormally high blood pressure, is a major risk factor for heart attack, stroke, and kidney failure. The Epithelial Sodium Channel (ENaC), one of the main transporters regulates blood pressure by tightly controlling the sodium reabsorption along the nephron. Recently, we have shown an α-ENaC overexpression in platelets from hypertensive patients compared to platelets from normotensive subjects, suggesting it makes a contribution to the activation state of platelets and the physiopathology of hypertension. However, the involvement of the α-ENaC localized in neutrophils to this disease remains unknown. Neutrophils are the first leukocytes to be recruited to an inflammatory site and are equipped with a strong ability to eliminate intra- or extracellular pathogens using reactive oxygen species or antibacterial proteins contained in their granules.Using the Western blotting (Wb), flow cytometry, and qRT-PCR approaches; we determined α-ENaC neutrophil overexpression at the protein and messenger RNA (mRNA) levels. By confocal and cytometry analysis, we determined the α-ENaC distribution and the heterogeneity of HTN neutrophils population, respectively. Immunoprecipitation and Wb assays demonstrated the presence of both α-ENaC and caveolin-1 phosphorylated forms, compared with neutrophils from healthy individuals. Although neutrophils from hypertensive subjects circulating in an activated state were exhibiting important oxidative stress and modifications registered by confocal, atomic force, and scanning electron microscope, they conserved their defense capabilities. The features described above for neutrophils from hypertensive patients could be attributed to α-ENaC overexpression, as its drug inhibition diminished their activation state modulating the actin cytoskeleton reorganization triggered during the activation process. 相似文献
92.
Doris Döppes Gernot Rabeder Christine Frischauf Nadja Kavcik-Graumann Bernd Kromer Susanne Lindauer 《Historical Biology》2019,31(4):422-428
ABSTRACTCave bears have disappeared from the Alps from different altitudes at different times. The temporal progression of the HDEL (Height Dependent Extinction Line) – a compilation of the geologically most recent radiocarbon dates per altitude level – is not consistent with the general cooling of the temperatures from about 45 ka BP. The cave bear sites of the Northern Alps with the most recent radiocarbon ages are not situated in the lowlands but in caves in altitudes of 1,500 m to 1,700 m above sea level (a.s.l.).Cave bears fed almost exclusively on herbs and leaves. It was assumed that with the general cooling in the OIS 3 since about 45 ka BP also the migration of the alpine elements into the lowlands took place. It could be recognized that the populations in the lower situated cave bear site became earlier extinct than the cave bear population in the higher altitudes.With new radiocarbon dates, done at the Curt-Engelhorn-Center Archaeometry at the Reiss-Engelhorn-Museen in Mannheim (Germany), the HDEL can be determined much more precisely and the causes of gradual extinction are also better understood. 相似文献
93.
P A Doris 《Peptides》1988,9(3):481-485
Push-pull perfusion of the hypothalamic paraventricular nucleus in sodium pentobarbital anesthetized Sprague-Dawley rats indicates the release of angiotensin II-immunoreactive material in this area. Attempts to demonstrate a neuronal origin of this material by chemical depolarization with perfusate containing either 40 or 120 mM K+ were unsuccessful. However, this material does appear to be of central origin since intravenous infusion of arginine-vasopressin, a similar sized peptide, did not result in the appearance of increased levels of this substrate in the perfusate, indicating that the integrity of the blood-brain barrier was not compromised by the perfusion. 相似文献
94.
A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes 总被引:19,自引:0,他引:19
Bánfi B Molnár G Maturana A Steger K Hegedûs B Demaurex N Krause KH 《The Journal of biological chemistry》2001,276(40):37594-37601
Superoxide and its derivatives are increasingly implicated in the regulation of physiological functions from oxygen sensing and blood pressure regulation to lymphocyte activation and sperm-oocyte fusion. Here we describe a novel superoxide-generating NADPH oxidase referred to as NADPH oxidase 5 (NOX5). NOX5 is distantly related to the gp91(phox) subunit of the phagocyte NADPH oxidase with conserved regions crucial for the electron transport (NADPH, FAD and heme binding sites). However, NOX5 has a unique N-terminal extension that contains three EF hand motifs. The mRNA of NOX5 is expressed in pachytene spermatocytes of testis and in B- and T-lymphocyte-rich areas of spleen and lymph nodes. When heterologously expressed, NOX5 was quiescent in unstimulated cells. However, in response to elevations of the cytosolic Ca(2+) concentration it generated large amounts of superoxide. Upon Ca(2+) activation, NOX5 also displayed a second function: it became a proton channel, presumably to compensate charge and pH alterations due to electron export. In summary, we have identified a novel NADPH oxidase that generates superoxide and functions as a H(+) channel in a Ca(2+)-dependent manner. NOX5 is likely to be involved in Ca(2+)-activated, redox-dependent processes of spermatozoa and lymphocytes such as sperm-oocyte fusion, cell proliferation, and cytokine secretion. 相似文献
95.
Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters 总被引:5,自引:0,他引:5
There is strong evidence supporting the deleterious effects of aging on learning and memory and behavioral parameters in normal mice. However, little is known about the Ames dwarf mouse, which has a Prop-1 gene mutation resulting in deficiencies in growth hormone, thyroid-stimulating hormone, and prolactin. These mice are much smaller and live significantly longer than their normal siblings. Using the elevated plus-maze, locomotor activity meters, and an inhibitory avoidance learning task, the present study compared Ames dwarf mice to their normal siblings. Results showed that Ames dwarf mice did not experience an age-related decline in locomotor activity when compared to their young counterparts. Furthermore, old dwarf mice did not differ from the young groups in inhibitory avoidance retention, while old normal animals performed more poorly than both young groups on this test. Elevated plus-maze behavior did not differ in the old normal versus dwarf groups, but the old groups did differ from the young. Results indicate that both old groups experienced a significant decline in anxiety with age. Taken together, these results indicate that multiple hormone deficiencies resulting from a lack of primary pituitary function have beneficial effects on cognitive function and locomotor behavior in advanced age. In fact, the Ames dwarf mouse may provide a model for studies of delayed mental as well as physical aging. 相似文献
96.
97.
98.
Bartke A Chandrashekar V Turyn D Steger RW Debeljuk L Winters TA Mattison JA Danilovich NA Croson W Wernsing DR Kopchick JJ 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1999,222(2):113-123
Transgenic mice overexpressing growth hormone (GH) exhibit alterations in the function of the hypothalamic-pituitary-gonadal (HPG) axis and the H-P-adrenal axis. Alterations in the turnover of hypothalamic neurotransmitters, in plasma hormone levels, and in regulation of their release are associated with reproductive deficits, particularly in females. Results reported after publication of our minireview on this subject provided evidence that GH-transgenic mice have increased binding of GH to GH binding proteins in plasma, are hyperinsulinemic and insulin resistant, and have major alterations in energy budgets with increased allocation to growth. Reduced life span and fertility of these animals may be related to insufficient allocation of energy to reproduction and maintenance. Growth hormone resistance induced by transgenic expression of an antagonistic bGH analog or by targeted disruption (knock-out, KO) of the GH receptor (GH-R) gene leads to dramatic suppression of plasma levels of insulin-like growth factor-1 (IGF-1), and dwarf phenotype due to reduced growth and increased adiposity. In both models of GH resistance, there are marked reproductive deficits in females, decline of breeding performance of males, and alterations in the function of the HPG axis. In GH-R-KO females, puberty is delayed, and litter size is reduced. Fetal weights are reduced whereas placental weights are increased, and the weight of newborn pups is reduced despite an increase in the length of gestation. In GH-R-KO males, copulatory behavior and fertility are reduced, plasma PRL is elevated, and responses to luteinizing hormone releasing hormone (LHRH) in vivo and to LH in vitro are suppressed. However, reproductive deficits in GH-R-KO mice are very mild when compared to those described previously in IGF-KO animals. Apparently, the amounts of IGF-1 that may be produced locally in the absence of GH stimulation are sufficient for sexual maturation and fertility in both sexes, whereas quantitative deficits in reproductive function reflect absence of GH-dependent IGF-1 production and other consequences of eliminating GH signaling. The reproduction phenotype of the GH-R-KO mice is also mild when compared to dwarf mice that lack GH, prolactin (PRL), and thyroid stimulating hormone (TSH). This is presumably related to the presence of redundant mechanisms in the stimulatory control of the gonads by the pituitary and the ability of animals capable of producing PRL and TSH to compensate partially for the absence of GH signaling. 相似文献
99.
100.
Nitric oxide (NO)-sensitive guanylyl-cyclase (GC) is the most important receptor for the signaling molecule NO. Activation of the enzyme is brought about by binding of NO to the prosthetic heme group. By monitoring NO-binding and catalytic activity simultaneously, we show that NO activates GC only if the reaction products of the enzyme are present. NO-binding in the absence of the products did not activate the enzyme, but yielded a nonactivated species with the spectral characteristics of the active form. Conversion of the nonactivated into the activated conformation of the enzyme required the simultaneous presence of NO and the reaction products. Furthermore, the products magnesium/cGMP/pyrophosphate promoted the release of the histidine-iron bond during NO-binding, indicating reciprocal communication of the catalytic and ligand-binding domains. Based on these observations, we present a model that proposes two NO-bound states of the enzyme: an active state formed in the presence of the products and a nonactivated state. The model not only covers the data reported here but also consolidates results from previous studies on NO-binding and dissociation/deactivation of GC. 相似文献