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61.
The force-length relationship is a basic property of skeletal muscle. Knowledge of this relationship is necessary for most analyses of human movement, and in simulation models predicting movement control strategies. Studies on animal muscles have shown that force-length relationships for sub-maximal contractions are not related through a simple scaling procedure to the relationship for maximal contractions. Furthermore, potentiation might produce a shift of sub-maximal relative to maximal force-length relationships. In this study, we tested the hypothesis that human force-elbow angle relationships for sub-maximal unpotentiated contractions are shifted to larger elbow angles (i.e. larger muscle lengths) compared to the relationship for maximal voluntary contractions (MVC), and that this shift is reduced, or even abolished, for sub-maximal potentiated contractions. Force-elbow angle relationships (48-160 degrees) were obtained from healthy subjects (n=13). At each of nine tested elbow angles, the test set consisted of a single twitch (ST(pre)) and a doublet twitch (DT(pre)) stimulation of m. biceps brachii, followed by an MVC, followed by another single twitch (ST(post)) and a doublet twitch (DT(post)) stimulation. The single and doublet twitches induced sub-maximal contractions. The force-elbow angle relationships for the pre-MVC (unpotentiated) twitch contractions were shifted to larger angles compared to those obtained for MVC. The force-elbow angle relationships for the post-MVC (potentiated) twitch contractions were shifted to smaller angles compared to those obtained for the unpotentiated twitch contractions. These results support the idea that the shift to larger muscle lengths for the sub-maximal, unpotentiated force-length relationships relative to the relationship for maximal contractions may be caused by a length-dependent Ca(2+) sensitivity that may be offset, at least in part, by potentiation. 相似文献
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63.
Herzog W Zeng X Lele Z Sonntag C Ting JW Chang CY Hammerschmidt M 《Developmental biology》2003,254(1):36-49
Formation of the adenohypophysis in mammalian embryos occurs via an invagination of the oral ectoderm to form Rathke's pouch, which becomes exposed to opposing dorsoventral gradients of signaling proteins governing specification of the different hormone-producing pituitary cell types. One signal promoting pituitary cell proliferation and differentiation to ventral cell types is Sonic hedgehog (Shh) from the oral ectoderm. To study pituitary formation and patterning in zebrafish, we cloned four cDNAs encoding different pituitary hormones, prolactin (prl), proopiomelancortin (pomc), thyroid stimulating hormone (tsh), and growth hormone (gh), and analyzed their expression patterns relative to that of the pituitary marker lim3. prl and pomc start to be expressed at the lateral edges of the lim3 expression domain, before pituitary cells move into the head. This indicates that patterning of the pituitary anlage and terminal differentiation of pituitary cells starts while cells are still organized in a placodal fashion at the anterior edge of the developing brain. Following the expression pattern of prl and pomc during development, we show that no pituitary-specific invagination equivalent to Rathke's pouch formation takes place. Rather, pituitary cells move inwards together with stomodeal cells during oral cavity formation, with medial cells of the placode ending up posterior and lateral cells ending up anterior, resulting in an anterior-posterior, rather than a dorsoventral, patterning of the adenohypophysis. Carrying out loss- and gain-of-function experiments, we show that Shh from the ventral diencephalon plays a crucial role during induction, patterning, and growth of the zebrafish adenohypophysis. The phenotypes are very similar to those obtained upon pituitary-specific inactivation or overexpression of Shh in mouse embryo, suggesting that the role of Shh during pituitary development has been largely conserved between fish and mice, despite the different modes of pituitary formation in the two vertebrate classes. 相似文献
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Cardiac function in neuropeptide Y Y4 receptor-knockout mice 总被引:1,自引:0,他引:1
Autonomic control of cardiovascular function in neuropeptide Y (NPY) Y4 receptor-knockout mice was investigated using pancreatic polypeptide (PP), NPY and specific agonists and antagonists for other NPY receptors well characterised in cardiovascular function. Y4 receptor-knockout mice, anaesthetised with sodium pentobarbitone, displayed slower heart rate, indicated by a higher pulse interval and lower blood pressure compared to control mice. After vagus nerves were cut heart rate increased but was still significantly slower than in control mice. PP had no effect on blood pressure or cardiac vagal activity in either group of mice, which was consistent with earlier studies in other species. Injection of NPY evoked an increase in blood pressure but the response was significantly reduced in Y4 receptor-knockout mice compared to the controls. The reduction in pressor activity was not Y1 mediated as the selective Y1 antagonist, BIBP 3226, was effective in blocking NPY pressor activity in knockout mice. In addition, cardiac vagal inhibitory activity evoked by low doses of NPY was also reduced when compared to control responses. As N-acetyl [Leu(28, 31)] NPY 24-36 inhibited vagal activity dose dependently in both groups of mice with no difference in response at any dose, it is unlikely that this effect also is receptor mediated. We propose that the reduced vasoconstrictor and vagal inhibitory activity evoked by NPY in Y4 receptor-knockout mice is due to a lack of adrenergic tone bought about by a proposed reduction in sympathetic activity, possibly resulting from altered NPY activity secondarily affecting adrenergic transmission. We conclude that Y4 receptor deletion disrupts autonomic balance within the cardiovascular system. 相似文献
66.
Inhibitory effects of central neuropeptide Y on the somatotropic and gonadotropic axes in male rats are independent of adrenal hormones 总被引:6,自引:0,他引:6
Neuropeptide Y (NPY) in the hypothalamus exerts multiple physiological functions including stimulation of adipogenic pathways such as feeding and insulin secretion as well as inhibition of the somatotropic and gonadotropic axes. Since hypothalamic NPY-ergic activity is increased by negative energy balance, NPY enables coordinated regulation of growth and reproduction in parallel with energy availability. Chronic pathological increases in central NPY-ergic activity contribute to obesity. Many of the adipogenic effects of NPY are specifically dependent on adrenal glucocorticoids. However, in the current study we show that central NPY does not require adrenal hormones to inhibit the somatotropic and gonadotropic axes in rats. Male adrenalectomized and sham-operated normal rats were intracerebroventricularly (ICV) infused with NPY (15 microg/day) or saline for 5-7 days, and plasma leptin, insulin-like growth factor (IGF-1) and testosterone were assayed, and epididymal white adipose tissue (WATe) was weighed. In normal intact rats, WATe weight and leptinemia were significantly increased by NPY, and these effects were prevented by adrenalectomy. In normal rats, NPY markedly reduced plasma IGF-1 levels (470 +/- 40 versus 1260 +/- 90 ng/ml) and testosterone (0.53 +/- 0.28 versus 5.4 +/- 0.80 nmol/l in saline-infused controls, p < 0.0001). Adrenalectomy decreased plasma IGF-1 concentrations to 290 +/- 30 (p < 0.0001 versus normal rats), which were significantly reduced further by NPY. However, adrenalectomy had no significant effect on basal nor on NPY-induced plasma testosterone concentrations. In conclusion unlike the stimulatory effects of NPY on fat mass and leptinemia, NPY-induced inhibition of the somatotropic and gonadotropic axes in male rats do not require adrenal hormones. 相似文献
67.
Force depression following muscle shortening was investigated in cat soleus (n=6) at 37 degrees C for a variety of contractile conditions with the aim to test the hypotheses that force depression was independent of the speed of shortening and was directly related to the mechanical work produced by the muscle during shortening. Force depression was similar for tests in which the mechanical work performed by the muscle was similar, independent of the speed of shortening (range of speeds: 4-256mm/s). On the other hand, force depression varied significantly at a given speed of shortening but different amounts of mechanical work, supporting the hypothesis that force depression was not speed - but work dependent. The variations in the mechanical work produced by the muscle during shortening accounted for 87-96% of the variance observed in the force depression following shortening further supporting the idea that the single scalar variable work accounts for most of the observed loss in isometric force after shortening. The results of the present study are also in agreement with the notion that the mechanism underlying force depression might be associated with an inhibition of cross-bridge attachments in the overlap zone formed during the shortening phase, as proposed previously (Herzog and Leonard, 1997. Journal of Bimechanics 30 (9), 865-872; Maréchal and Plaghki, 1979. 相似文献
68.
Neuropilin-2 is a receptor for the vascular endothelial growth factor (VEGF) forms VEGF-145 and VEGF-165 [corrected 总被引:1,自引:0,他引:1
Gluzman-Poltorak Z Cohen T Herzog Y Neufeld G 《The Journal of biological chemistry》2000,275(24):18040-18045
Neuropilin-1 (np-1) and neuropilin-2 (np-2) are receptors for axon guidance factors belonging to the class 3 semaphorins. np-1 also binds to the 165-amino acid heparin-binding form of VEGF (VEGF(165)) but not to the shorter VEGF(121) form, which lacks a heparin binding ability. We report that human umbilical vein-derived endothelial cells express the a17 and a22 splice forms of the np-2 receptor. Both np-2 forms bind VEGF(165) with high affinity in the presence of heparin (K(D) 1.3 x 10(-10) m) but not VEGF(121). np-2 also binds the heparin-binding form of placenta growth factor. These binding characteristics resemble those of np-1. VEGF(145) is a secreted heparin binding VEGF form that contains the peptide encoded by exon 6 of VEGF but not the peptide encoded by exon 7, which is present in VEGF(165). VEGF(145) binds to np-2 with high affinity (K(D) 7 x 10(-10) m). Surprisingly, VEGF(145) did not bind to np-1. Indeed, VEGF(145) does not bind to MDA-MB-231 breast cancer cells, which predominantly express np-1. By contrast, VEGF(145) binds to human umbilical vein-derived endothelial cells, which express both np-1 and np-2. The binding of VEGF(165) to porcine aortic endothelial cells expressing recombinant np-2 did not affect the proliferation or migration of the cells. Nevertheless, it is possible that VEGF-induced np-2-mediated signaling will take place only in the presence of other VEGF receptors such as VEGF receptor-1 or VEGF receptor-2. 相似文献
69.
McCrea K Wisialowski T Cabrele C Church B Beck-Sickinger A Kraegen E Herzog H 《Regulatory peptides》2000,87(1-3):47-58
Members of the neuropeptide Y (NPY) family regulate many physiological processes via interaction with at least four functional, pharmacologically distinct Y-receptors. However, selective antagonists developed for several subtypes have not been useful in defining particular Y-receptor functions in vivo. To identify critical residues within members of the NPY family required for Y-receptor subtype-selectivity we have determined the contribution of each residue within NPY to receptor binding by replacing them with L-alanine. In a second study, chimeric peptides where single or stretches of residues were interchanged between members of the NPY family were generated and tested in radioligand binding studies. Overall, substituted alanine analogues exhibited similar orders of affinities at each Y-receptor subtype with no obvious subtype-selectivity. Residues of particular interest are Leu30 which exhibited selectivity for the Y4-receptor, whereas Asp16 does not appear to play any role in ligand binding. Several chimeric peptides, e.g., [K4]pancreatic polypeptide ([K4]PP) and [RYYSA(19-23)]PP clearly showed higher affinity at the Y4 and Y5 subtypes compared to the Y1 and Y2 subtypes. In addition, the transfer of a proline residue from position 14 to 13 in peptide YY decreases its affinity at the Y1-, Y4- and Y5-receptors but is unchanged at the Y2 subtype. Combining these results, and with the help of molecular modelling, second generation chimeras were designed. The most significant improvement was achieved in chimera 2-36[K4,RYYSA(19-23)]PP where the affinity for the Y5 subtype increased by ninefold over that from NPY. Several of these compounds were also tested for their ability to stimulate food intake in a rat model. Interestingly, again 2-36[K4,RYYSA(19-23)]PP showed the most dramatic effect with a major increase on food intake over a range of doses compared to NPY suggesting a possible synergistic effect of several Y-receptors on feeding behaviour. 相似文献
70.