全文获取类型
收费全文 | 748篇 |
免费 | 48篇 |
国内免费 | 2篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 26篇 |
2020年 | 11篇 |
2019年 | 8篇 |
2018年 | 16篇 |
2017年 | 12篇 |
2016年 | 31篇 |
2015年 | 44篇 |
2014年 | 45篇 |
2013年 | 64篇 |
2012年 | 57篇 |
2011年 | 76篇 |
2010年 | 50篇 |
2009年 | 41篇 |
2008年 | 52篇 |
2007年 | 46篇 |
2006年 | 36篇 |
2005年 | 49篇 |
2004年 | 27篇 |
2003年 | 16篇 |
2002年 | 19篇 |
2001年 | 3篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1992年 | 5篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1985年 | 3篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1949年 | 1篇 |
排序方式: 共有798条查询结果,搜索用时 15 毫秒
1.
Binding and internalization of atrial natriuretic factor by high-affinity receptors in A10 smooth muscle cells 总被引:1,自引:0,他引:1
A10 smooth muscle cells, derived from embryonic rat thoracic aorta, responded to the atrial natriuretic factor (ANF) with increased levels of cyclic GMP. These cells possess high-affinity (apparent Kd = 50 pM) plasma membrane receptors for ANF. Internalization of ANF at 37 degrees C was indicated by the following: approximately 25% of the 125I-ANF associated with the cells at elevated temperatures could not be dissociated from the surface of the cells, but could be released by permeabilization with saponin, and the amount of nondissociable ANF increased in the presence of chloroquine. In whole cells and in membranes, a single polypeptide of 60,000 Da was specifically labeled by a photoaffinity analog of 125I-ANF, as well as by crosslinking, and an IC50 of 80 pM for inhibition of the labeling by ANF was observed. The ANF receptor in A10 cells was distinguished from that in rabbit aorta by its high affinity for shorter and linear analogs of ANF, as well as by a different photolabeling pattern. 相似文献
2.
The selectivity of statine-based inhibitors against various human aspartic proteinases. 总被引:7,自引:0,他引:7 下载免费PDF全文
R A Jupp B M Dunn J W Jacobs G Vlasuk K E Arcuri D F Veber D S Perlow L S Payne J Boger S de Laszlo et al. 《The Biochemical journal》1990,265(3):871-878
The interactions of five human enzymes (renin, pepsin, gastricsin, cathepsin D and cathepsin E) and the aspartic proteinase from Endothia parasitica with several series of synthetic inhibitors were examined. All of the inhibitors contained the dipeptide analogue statine or its phenylalanine or cyclohexylalanine homologues in the P1-P1' positions. The residues occupying the peripheral sub-sites (P4 to P3') were varied systematically and inhibitory constants were determined for the interactions with each of the proteinases. Inhibitors were elucidated that specifically inhibited human renin and did not affect any of the other human enzymes or the fungal proteinase. With suitable selection of residues to occupy individual sub-sites, effective inhibitors of specific human aspartic proteinases may now be designed. 相似文献
3.
Milford H. Wolpoff Fred H. Smith Mirko Malez Jakov Radov
i Darko Rukavina 《American journal of physical anthropology》1981,54(4):499-545
Human remains excavated from Vindija cave include a large although fragmentary sample of late Mousterian-associated specimens and a few additional individuals from the overlying early Upper Paleolithic levels. The Mousterian-associated sample is similar to European Neandertals from other regions. Compared with earlier Neandertals from south central Europe, this sample evinces evolutionary trends in the direction of Upper Paleolithic Europeans. Compared with the western European Neandertals, the same trends can be demonstrated, although the magnitude of difference is less, and there is a potential for confusing temporal with regional sources of variation. The early Upper Paleolithic-associated sample cannot be distinguished from the Mousterian-associated hominids. We believe that this site provides support for Hrdli?ka's “Neandertal phase” of human evolution, as it was originally applied in Europe. 相似文献
4.
Grzegorz Garbacz Bartosz Kołodziej Mirko Koziolek Werner Weitschies Sandra Klein 《AAPS PharmSciTech》2013,14(2):517-522
The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of carbon dioxide (CO2) from the solution results in an uncontrolled increase of the pH. In order to maintain the pH on the desired level, either a CO2 loss must be completely avoided or the escaped CO2 has to be replaced by quantitative substitution, i.e. feeding the solution with the respective amount of gas, which re-acidifies the buffer after dissociation. The present work aimed at the development of a device enabling an automatic pH monitoring and regulation of hydrogen carbonate buffers during dissolution tests. 相似文献
5.
Genea Edwards Jennifer Arcuri Haiyan Wang Noel Ziebarth Gulab Zode Richard K. Lee Sanjoy K. Bhattacharya 《Journal of cellular and molecular medicine》2020,24(7):3856-3900
Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary open-angle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data for above classes of lipids. We standardized in vitro assays for rapid characterization of lipids undergoing significant diminishment in disease state. Evaluation of lipids using in vitro assays helped select a finite number of lipids that may potentially expand cellular interstitial space embedded in an artificial matrix or increase fluid flow across a layer of cells. These assays reduced a number of lipids for initial evaluation using a mouse model, DBA/2J with spontaneous IOP elevation. These lipids were then used in other mouse models for confirmation of IOP lowering potential of a few lipids that were found promising in previous assessments. Our results provide selected lipid molecules that can be pursued for further evaluation and studies that may provide insight into their function. 相似文献
6.
Rosangela Catoni Francesco Bracco Mirko U. Granata 《Physiology and Molecular Biology of Plants》2020,26(2):261-270
Mesophyll conductance (gm) has received over time much less attention than stomatal conductance (gs), although it affects leaf photosynthesis to about the same extent as stomatal conductance does. The objective of this study was to analyze the gm trend in five understory herbaceous species growing in a close-canopy forest in the north-west of Italy. In particular, three of analyzed species were monocots: Carex brizoides Lam., Carex pilosa Scop., and Oplismenus undulatifolius P. Beauv and the others dicots species: Circaea lutetiana L., and Pulmonaria officinalis Ced. The results showed, on one hand, the absence of correlation between gm and the considered environmental variables in the forest understory (i.e. air temperature, photosynthetic photon flux density and carbon dioxide concentration). Moreover, we carried out a principal component analysis considering all the analyzed morphological and physiological variables for the five species. The following correlation between the first component, related to the leaf mass per unit of leaf area and the leaf tissue density, and gm seem to suggest a key role of the leaf structural features in determining gm variations across the five species. 相似文献
7.
Integrated requirement of non‐specific and sequence‐specific DNA binding in Myc‐driven transcription
8.
9.
Marilisa Villano Annalisa Borghini Mirko Manetti Erica Gabbrielli Antonella Rossi Piersante Sestini Anna Franca Milia Francesca Nacci Serena Guiducci Marco Matucci-Cerinic Lidia Ibba-Manneschi Elisabetta Weber 《Arthritis research & therapy》2013,15(4):R90
Introduction
Systemic sclerosis (SSc) is a connective tissue disorder characterized by endothelial cell injury, autoimmunity and fibrosis. The following three fibrillin-1 alterations have been reported in SSc. (1) Fibrillin-1 microfibrils are disorganized in SSc dermis. (2) Fibrillin-1 microfibrils produced by SSc fibroblasts are unstable. (3) Mutations in the FBN1 gene and anti-fibrillin-1 autoantibodies have been reported in SSc. Fibrillin-1 microfibrils, which are abundantly produced by blood and lymphatic microvascular endothelial cells (B-MVECs and Ly-MVECs, respectively), sequester in the extracellular matrix the latent form of the potent profibrotic cytokine transforming growth factor β (TGF-β). In the present study, we evaluated the effects of SSc sera on the deposition of fibrillin-1 and microfibril-associated glycoprotein 1 (MAGP-1) and the expression of focal adhesion molecules by dermal B-MVECs and Ly-MVECs.Methods
Dermal B-MVECs and Ly-MVECs were challenged with sera from SSc patients who were treatment-naïve or under cyclophosphamide (CYC) treatment and with sera from healthy controls. Fibrillin-1/MAGP-1 synthesis and deposition and the expression of αvβ3 integrin/phosphorylated focal adhesion kinase and vinculin/actin were evaluated by immunofluorescence and quantified by morphometric analysis.Results
Fibrillin-1 and MAGP-1 colocalized in all experimental conditions, forming a honeycomb pattern in B-MVECs and a dense mesh of short segments in Ly-MVECs. In B-MVECs, fibrillin-1/MAGP-1 production and αvβ3 integrin expression significantly decreased upon challenge with sera from naïve SSc patients compared with healthy controls. Upon challenge of B-MVECs with sera from CYC-treated SSc patients, fibrillin-1/MAGP-1 and αvβ3 integrin levels were comparable to those of cells treated with healthy sera. Ly-MVECs challenged with SSc sera did not differ from those treated with healthy control sera in the expression of any of the molecules assayed.Conclusions
Because of the critical role of fibrillin-1 in sequestering the latent form of TGF-β in the extracellular matrix, its decreased deposition by B-MVECs challenged with SSc sera might contribute to dermal fibrosis. In SSc, CYC treatment might limit fibrosis through the maintenance of physiologic fibrillin-1 synthesis and deposition by B-MVECs. 相似文献10.