全文获取类型
收费全文 | 304篇 |
免费 | 15篇 |
出版年
2020年 | 2篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 6篇 |
2014年 | 5篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 19篇 |
2010年 | 9篇 |
2009年 | 10篇 |
2008年 | 15篇 |
2007年 | 12篇 |
2006年 | 3篇 |
2005年 | 13篇 |
2004年 | 14篇 |
2003年 | 11篇 |
2002年 | 6篇 |
2001年 | 8篇 |
2000年 | 15篇 |
1999年 | 7篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1972年 | 3篇 |
1921年 | 2篇 |
1908年 | 7篇 |
1900年 | 2篇 |
1899年 | 3篇 |
1898年 | 2篇 |
1897年 | 4篇 |
1895年 | 6篇 |
1894年 | 7篇 |
1893年 | 2篇 |
1892年 | 2篇 |
1891年 | 5篇 |
1888年 | 2篇 |
排序方式: 共有319条查询结果,搜索用时 187 毫秒
71.
Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules 总被引:18,自引:4,他引:14 下载免费PDF全文
Chemical cross-linking and gel permeation chromatography were used to examine early events in the biogenesis of class I histocompatibility molecules. We show that newly synthesized class I heavy chains associate rapidly and quantitatively with an 88-kD protein in three murine tumor cell lines. This protein (p88) does not appear to possess Asn-linked glycans and it is not the abundant ER protein, GRP94. The class I-p88 complex exists transiently (t1/2 = 20-45 min depending on the specific class I heavy chain) and several lines of evidence suggest that p88 dissociates from the complex while still in the ER. Dissociation is not triggered upon binding of beta 2-microglobulin to the heavy chain (t1/2 = 2-5 min). However, the rate of dissociation does correlate with the characteristic rate of ER to Golgi transport for the particular class I molecule studied. Consequently, dissociation of p88 may be rate limiting for ER to Golgi transport. Class I molecules bind antigenic peptides, apparently in the ER, for subsequent presentation to cytotoxic T lymphocytes at the cell surface. p88 could promote peptide binding or it may retain class I molecules in the ER during formation of the ternary complex of heavy chain, beta 2-microglobulin, and peptide. 相似文献
72.
Nucleotide sequence of the gene for human prothrombin 总被引:23,自引:0,他引:23
A human genomic DNA library was screened for the gene coding for human prothrombin with a cDNA coding for the human protein. Eighty-one positive lambda phage were identified, and three were chosen for further characterization. These three phage hybridized with 5' and/or 3' probes prepared from the prothrombin cDNA. The complete DNA sequence of 21 kilobases of the human prothrombin gene was determined and included a 4.9-kilobase region that was previously sequenced. The gene for human prothrombin contains 14 exons separated by 13 intervening sequences. The exons range in size from 25 to 315 base pairs, while the introns range from 84 to 9447 base pairs. Ninety percent of the gene is composed of intervening sequence. All the intron splice junctions are consistent with sequences found in other eukaryotic genes, except for the presence of GC rather than GT on the 5' end of intervening sequence L. Thirty copies of Alu repetitive DNA and two copies of partial KpnI repeats were identified in clusters within several of the intervening sequences, and these repeats represent 40% of the DNA sequence of the gene. The size, distribution, and sequence homology of the introns within the gene were then compared to those of the genes for the other vitamin K dependent proteins and several other serine proteases. 相似文献
73.
74.
Dr. A. von Degen 《Plant Systematics and Evolution》1900,50(9):313-314
Ohne Zusammenfassung 相似文献
75.
76.
77.
Annemarie MM Vlaar Marinus JPG van Kroonenburgh Alfons GH Kessels Wim EJ Weber 《BMC neurology》2007,7(1):27
Background
Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre- and post-synaptic SPECT imaging in the differential diagnosis of PD. 相似文献78.
Using nine microsatellite loci, genetic diversity of small geographically isolated population of pedunculate oak Quercus robur L. (Fragaceae) was examined. The population was located outside of the species range in Bashkir Transuralia. Considerable
temporal dynamics of allelic diversity, explained in terms of different effectiveness of gene flow in different years, was
demonstrated. 相似文献
79.
Plasmin-mediated Proteolysis Is Required for Hepatocyte Growth Factor
Activation during Liver
Repair
Kumar Shanmukhappa Ursula Matte Jay L. Degen Jorge A. Bezerra 《The Journal of biological chemistry》2009,284(19):12917-12923
The physiological relevance of the activation of hepatocyte growth factor
(Hgf) by the plasminogen (Plg) system of proteases and its contribution to
tissue repair are largely undefined. Here, we investigated whether the
defective liver repair in mice lacking Plg is due to impaired activation of
Hgf. Loss of Plg in vivo suppressed Hgf activation and signaling
through its Met tyrosine kinase receptor. Without Plg, hepatocytes were
unresponsive to Hgf-induced proliferation and migration, with a more
pronounced impairment in hepatocyte movement within the hepatic environment.
Most notably, circumventing the defect in proteolytic activation of Hgf by the
downstream expression of an activated Met receptor corrected the functional
deficits and improved liver repair in Plg-deficient mice. These findings
support a fibrinolysis-unrelated role for Plg in modulating cell proliferation
and migration by activation of Hgf.Tissue repair requires a prompt proliferative response in concert with the
timely reorganization of the extracellular matrix. Each one of these processes
can be disrupted by the loss of individual growth factors or proteases, but
the precise regulatory relationship between these molecules in supporting
tissue repair is not fully understood. Multiple in vitro studies have
inferred that proteases in the plasminogen
(Plg)2 activation
system may be important in the proteolytic activation of the hepatocyte growth
factor (Hgf)
(1–4),
the ligand for the Met tyrosine kinase receptor that exerts potent mitogenic
and motogenic properties to mesenchymal and epithelial cells. This concept is
made even more attractive by the fact that Hgf is structurally related to Plg,
with multiple kringle domains and a catalytically inactive serine
protease-like domain. However, the physiological relevance of Plg to Hgf
activation and Hgf-related reparative processes are controversial and
effectively unexplored in vivo.We previously reported that a genetically imposed loss of circulating Plg
severely impairs clearance of necrotic cells and the repopulation of injured
zones by newly formed cells but without compromising the general hepatic
proliferative response (5).
Despite the indisputable role of Plg in fibrin clearance
(6), complementary studies in
mice with no capacity for fibrin deposition have shown that the loss of
fibrinolytic function alone in Plg-deficient mice cannot account for the
impediment in tissue repair
(5). Multiple nonfibrin targets
of plasmin-mediated proteolysis are known (e.g. serine and
metalloprotease zymogens, and extracellular matrix glycoproteins, latent
growth factors), and it is feasible that they may contribute to the focal
clearance of necrotic tissue. However, based on recent findings pointing to a
strikingly similar defect in hepatic repair in mice lacking Plg or a
conditional loss of Met (7), an
attractive hypothesis emerged that the Plg activation system supports
physiological liver repair by activation of the Met ligand, Hgf. Testing this
hypothesis, we found that the loss of Plg impairs Hgf activation, suppresses
Met phosphorylation and signaling, and prevents Hgf-induced migration of
hepatocytes. Most notably, consistent with a physiologically relevant
contribution of Plg to Hgf-Met signaling, the expression of an
autophosphorylated Met largely corrected the defective repair in Plg-deficient
livers. 相似文献
80.
Katherine Muñoz Victor Campos Meinolf Blaszkewicz Mario Vega Alejandro Alvarez Jorge Neira Gisela H. Degen 《Mycotoxin Research》2010,26(2):59-67
The mycotoxin ochratoxin A (OTA) and its metabolite ochratoxin alpha (OTα) were determined in milk and blood from nine lactating women who provided samples soon after delivery at a hospital in southern Chile. The analytical method applied liquid–liquid extraction with chloroform, and in the case of blood, an extra purification with solid phase extraction prior to HPLC analysis with fluorescence detection. OTA was detected in all human milk samples, with an average concentration of 106?±?45 ng/L (range 44–184 ng/L). Levels of OTα were 40?±?30 ng/L (LOQ 40 ng/L), but increased considerably upon enzymatic hydrolysis with ß-glucuronidase/sulfatase (up to 840?±?256 ng/L) in human milk. By contrast, there was no evidence for conjugates of OTA. The data on OTA in breast milk and levels reported in blood from women in Chile are indicative of an efficient lactational transfer of the mycotoxin. Infant exposure to OTA was estimated by considering their daily OTA intake with human milk at early stages of nursing. For the majority of milk samples, the calculated OTA intake of infants exceeded the tolerable daily intake (TDI) of 5 ng/kg body weight (bw)/day proposed by the Nordic Expert Group, and infant exposure approached the provisional tolerable doses of 14–16 ng/kg bw/day suggested by the Joint FAO/WHO Expert Committee on Food Additives (JEFCA) and by EFSA for adults. The present study documents and confirms the presence of OTA in human milk at levels where the TDI can be exceeded. These results point out the need to continue food and biological monitoring and to develop strategies, e.g. dietary recommendations to pregnant and lactating women, aimed to reduce OTA exposure in early periods of life. 相似文献