全文获取类型
收费全文 | 5271篇 |
免费 | 347篇 |
出版年
2023年 | 21篇 |
2021年 | 39篇 |
2020年 | 33篇 |
2019年 | 40篇 |
2018年 | 73篇 |
2017年 | 87篇 |
2016年 | 132篇 |
2015年 | 242篇 |
2014年 | 245篇 |
2013年 | 322篇 |
2012年 | 411篇 |
2011年 | 356篇 |
2010年 | 217篇 |
2009年 | 189篇 |
2008年 | 311篇 |
2007年 | 299篇 |
2006年 | 281篇 |
2005年 | 263篇 |
2004年 | 233篇 |
2003年 | 245篇 |
2002年 | 243篇 |
2001年 | 85篇 |
2000年 | 93篇 |
1999年 | 86篇 |
1998年 | 48篇 |
1997年 | 30篇 |
1996年 | 31篇 |
1995年 | 42篇 |
1994年 | 40篇 |
1993年 | 32篇 |
1992年 | 53篇 |
1991年 | 45篇 |
1990年 | 59篇 |
1989年 | 50篇 |
1988年 | 46篇 |
1987年 | 56篇 |
1986年 | 37篇 |
1985年 | 47篇 |
1984年 | 47篇 |
1983年 | 41篇 |
1982年 | 25篇 |
1981年 | 30篇 |
1980年 | 26篇 |
1979年 | 19篇 |
1978年 | 26篇 |
1974年 | 19篇 |
1973年 | 33篇 |
1972年 | 21篇 |
1971年 | 24篇 |
1970年 | 20篇 |
排序方式: 共有5618条查询结果,搜索用时 31 毫秒
1.
2.
Epithelial ovarian carcinoma (EOC), the major cause of gynaecological cancer death, is a heterogeneous disease classified into five subtypes. Each subtype has distinct clinical characteristics and is associated with different genetic risk factors and molecular events, but all are treated with surgery and platinum/taxane regimes. Tumour progression and chemoresistance is generally associated with major metabolic alterations, notably altered mitochondrial function(s). Here, we report for the first time that the expression of the mitochondrial regulators PGC1α and TFAM varies between EOC subtypes; furthermore, we have identified a profile in clear-cell carcinoma consisting of undetectability of PGC1α/TFAM, and low ERα/Ki-67. By contrast, high-grade serous carcinomas were characterised by a converse state of PGC1α/TFAM, ERα positivity and a high Ki-67 index. Interestingly, loss of PGC1α/TFAM and ERα was found also in a non-clear cell EOC cell line made highly resistant to platinum in vitro. Similar to clear-cell carcinomas, these resistant cells also showed accumulation of glycogen. Altogether, our data provide mechanistic insights into the chemoresistant nature of ovarian clear-cell carcinomas. Furthermore, these findings corroborate the need to take into account the diversity of EOC and to develop subtype specific treatment strategies. 相似文献
3.
4.
Influence of ionic strength and pH on the interaction between high-affinity heparin and antithrombin
Birgitta Nordenman Ingemar Björk 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,672(3):227-238
Binding constants for the binding of high-affinity heparin to antithrombin at different ionic strengths were determined by fluorescence titrations and were also estimated from dissociation curves of the heparin-antithrombin complex. These curves were monitored by near-ultraviolet circular dichroism or fluorescence. The dependence of the binding constant on the activity of NaCl suggested that maximally 5–6 charged groups are directly involved in the interaction between the two macromolecules. Major pH-dependent changes of the interaction, as evident by changes of the spectroscopic properties of the complex between the molecules, were found to occur below pH 5.5 and above pH 8.5. The acid change, which was irreversible, was most likely caused by an irreversible conformational change of antithrombin. At alkaline pH, however, the gross conformation of antithrombin was stable up to pH 12, while the affinity of high-affinity heparin for antithrombin began to decrease markedly at pH 8.5. The dissociation curve, which was reversible, had a midpoint around pH 9.5. This is compatible with the loss of affinity being caused by either a local conformational change, by ionization of tyrosine or by titration of one or more amino groups. 相似文献
5.
Strains of paramyxovirus type 1 (PMV-1) have been isolated from diseased racing pigeons in Sweden. One of these isolates was selected for studies of the pathogenicity and contagiousness in chickens. The same isolate was previously found to have a high intravenous pathogenicity index (IVPI) in 6 weeks old chickens. In three experiments it was found that the PMV-1 isolate was very pathogenic for 1 week old chickens but not pathogenic for 120 day old pullets inoculated intranasally and ocularly. Symptoms in the young chickens were similar to those seen in the neurotropic form of Newcastle disease. The mortality was high and the incubation period 5–11 days. The disease easily spread to young chickens kept in contact with diseased birds. The microscopic examination revealed an interstitial nonpurulent pneumonia and a nonpurulent encephalitis in the young chickens. In the pullets the only finding was a mild encephalitis. PMV-1 was recovered from all young chickens but not from the pullets. Both the chickens and the inoculated pullets developed antibodies to PMV-1. 相似文献
6.
Marine phytoplankton can evolve rapidly when confronted with aspects of climate change because of their large population sizes and fast generation times. Despite this, the importance of environment fluctuations, a key feature of climate change, has received little attention—selection experiments with marine phytoplankton are usually carried out in stable environments and use single or few representatives of a species, genus or functional group. Here we investigate whether and by how much environmental fluctuations contribute to changes in ecologically important phytoplankton traits such as C:N ratios and cell size, and test the variability of changes in these traits within the globally distributed species Ostreococcus. We have evolved 16 physiologically distinct lineages of Ostreococcus at stable high CO2 (1031±87 μatm CO2, SH) and fluctuating high CO2 (1012±244 μatm CO2, FH) for 400 generations. We find that although both fluctuation and high CO2 drive evolution, FH-evolved lineages are smaller, have reduced C:N ratios and respond more strongly to further increases in CO2 than do SH-evolved lineages. This indicates that environmental fluctuations are an important factor to consider when predicting how the characteristics of future phytoplankton populations will have an impact on biogeochemical cycles and higher trophic levels in marine food webs. 相似文献
7.
R H?kanson D Chen E Lindstr?m P Norlén M Bj?rkqvist D Lehto-Axtelius 《The Yale journal of biology and medicine》1998,71(3-4):163-171
The enterochromaffin-like (ECL) cells of the oxyntic mucosa (fundus) of the stomach produce, store and secrete histamine, chromogranin A-derived peptides such as pancreastatin, and an unanticipated but as yet unidentified peptide hormone. The cells are stimulated by gastrin and pituitary adenylate cyclase activating peptide and suppressed by somatostatin and galanin. Choline esters and histamine seem to be without effect on ECL cell secretion. The existence of a gastrin-ECL cell axis not only explains how gastrin stimulates acid secretion but also may help to explore the functional significance of the ECL cells with respect to the nature and bioactivity of its peptide hormone. From the results of studies of gastrectomized/fundectomized and gastrin-treated rats, it has been speculated that the anticipated ECL-cell peptide hormone acts on bone metabolism. 相似文献
8.
Effects of eccentric exercise on the immune system in men 总被引:10,自引:0,他引:10
The effects of eccentric exercise on changes innumbers of circulating leukocytes, cell activation, cell adhesion, andcellular memory function were investigated in 12 men, aged 22-35yr. The immunologic effects of postexercise epidermal treatment withmonochromatic, infrared light were also evaluated. Blood was drawnbefore and 6, 24, and 48 h after exercise for phenotyping and analysisof creatine kinase activity. There was an increase in leukocyte, monocyte, and neutrophil number, no change in the number of basophils, eosinophils, B cells, and T cells, and a decrease in natural killer cell number postexercise. Some markers of lymphocyte and monocyte activation remained unchanged or decreased, whereas the expression ofadhesion molecules 62L and 11b increased on monocytes. It is concludedthat eccentric exercise induced decreased activation, and increasedcell adhesion capacity, of monocytes. Altered trafficking of cellsbetween lymphoid tissue and blood, selective apoptosis, orattachment/detachment from the endothelial wall can explain theobserved phenotypic changes. Treatment with monochromatic, infraredlight did not significantly affect any of the investigated variables.Correlations between immunologic and physiological parameters indicatea role of the immune system in adaptation to physical exercise. 相似文献
9.
Adnan Cavka Bj?rn Alriksson Shaunita H. Rose Willem H. van Zyl Leif J. J?nsson 《Journal of industrial microbiology & biotechnology》2011,38(8):891-899
The possibility to utilize fiber sludge, waste fibers from pulp mills and lignocellulose-based biorefineries, for combined production of liquid biofuel and biocatalysts was investigated. Without pretreatment, fiber sludge was hydrolyzed enzymatically to monosaccharides, mainly glucose and xylose. In the first of two sequential fermentation steps, the fiber sludge hydrolysate was fermented to cellulosic ethanol with the yeast Saccharomyces cerevisiae. Although the final ethanol yields were similar, the ethanol productivity after 9.5?h was 3.3?g/l/h for the fiber sludge hydrolysate compared with only 2.2?g/l/h for a reference fermentation with similar sugar content. In the second fermentation step, the spent fiber sludge hydrolysate (the stillage obtained after distillation) was used as growth medium for recombinant Aspergillus niger expressing the xylanase-encoding Trichoderma reesei (Hypocrea jecorina) xyn2 gene. The xylanase activity obtained with the spent fiber sludge hydrolysate (8,500?nkat/ml) was higher than that obtained in a standard medium with similar monosaccharide content (1,400?nkat/ml). Analyses based on deglycosylation with N-glycosidase?F suggest that the main part of the recombinant xylanase was unglycosylated and had molecular mass of 20.7?kDa, while a minor part had N-linked glycosylation and molecular mass of 23.6?kDa. Chemical analyses of the growth medium showed that important carbon sources in the spent fiber sludge hydrolysate included xylose, small aliphatic acids, and oligosaccharides. The results show the potential of converting waste fiber sludge to liquid biofuel and enzymes as coproducts in lignocellulose-based biorefineries. 相似文献
10.
Hanna Gladh Erika Bergsten Folestad Lars Muhl Monika Ehnman Philip Tannenberg Anna-Lisa Lawrence Christer Betsholtz Ulf Eriksson 《PloS one》2016,11(3)
Platelet-derived growth factor D (PDGF-D) is the most recently discovered member of the PDGF family. PDGF-D signals through PDGF receptor β, but its biological role remains largely unknown. In contrast to other members of the PDGF family of growth factors, which have been extensively investigated using different knockout approaches in mice, PDGF-D has until now not been characterized by gene inactivation in mice. Here, we present the phenotype of a constitutive Pdgfd knockout mouse model (Pdgfd-/-), carrying a LacZ reporter used to visualize Pdgfd promoter activity. Inactivation of the Pdgfd gene resulted in a mild phenotype in C57BL/6 mice, and the offspring was viable, fertile and generally in good health. We show that Pdgfd reporter gene activity was consistently localized to vascular structures in both postnatal and adult tissues. The expression was predominantly arterial, often localizing to vascular bifurcations. Endothelial cells appeared to be the dominating source for Pdgfd, but reporter gene activity was occasionally also found in subpopulations of mural cells. Tissue-specific analyses of vascular structures revealed that NG2-expressing pericytes of the cardiac vasculature were disorganized in Pdgfd-/- mice. Furthermore, Pdgfd-/- mice also had a slightly elevated blood pressure. In summary, the vascular expression pattern together with morphological changes in NG2-expressing cells, and the increase in blood pressure, support a function for PDGF-D in regulating systemic arterial blood pressure, and suggests a role in maintaining vascular homeostasis. 相似文献