全文获取类型
收费全文 | 3297篇 |
免费 | 220篇 |
国内免费 | 2篇 |
专业分类
3519篇 |
出版年
2024年 | 2篇 |
2023年 | 24篇 |
2022年 | 47篇 |
2021年 | 92篇 |
2020年 | 57篇 |
2019年 | 61篇 |
2018年 | 97篇 |
2017年 | 63篇 |
2016年 | 117篇 |
2015年 | 168篇 |
2014年 | 167篇 |
2013年 | 230篇 |
2012年 | 289篇 |
2011年 | 276篇 |
2010年 | 210篇 |
2009年 | 150篇 |
2008年 | 231篇 |
2007年 | 191篇 |
2006年 | 204篇 |
2005年 | 143篇 |
2004年 | 133篇 |
2003年 | 136篇 |
2002年 | 124篇 |
2001年 | 27篇 |
2000年 | 16篇 |
1999年 | 23篇 |
1998年 | 16篇 |
1997年 | 17篇 |
1996年 | 18篇 |
1995年 | 22篇 |
1994年 | 17篇 |
1993年 | 14篇 |
1992年 | 25篇 |
1991年 | 10篇 |
1990年 | 10篇 |
1989年 | 12篇 |
1988年 | 9篇 |
1987年 | 10篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 12篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1974年 | 5篇 |
1972年 | 5篇 |
1967年 | 2篇 |
1961年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有3519条查询结果,搜索用时 15 毫秒
51.
Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. 相似文献
52.
Ciborowski M Martin-Ventura JL Meilhac O Michel JB Ruperez FJ Tuñon J Egido J Barbas C 《Journal of proteome research》2011,10(3):1374-1382
Abdominal aortic aneurysm (AAA) is perma-nent and localized dilation of the abdominal aorta. Intraluminal thrombus (ILT) is involved in evolution and rupture of AAA. Complex biological processes associated with AAA include oxidative stress, proteolysis, neovascularization, aortic inflammation, cell death, and extracellular matrix breakdown. Biomarkers of growth and AAA rupture could give a more nuanced indication for surgery, unveil novel pathogenic pathways, and open possibilities for pharmacological inhibition of growth. Differential analysis of metabolites released by normal and pathological arteries in culture may help to find molecules that have a high probability of later being found in plasma and start signaling processes or be useful diagnostic/prognostic markers. We used a LC-QTOF-MS metabolomic approach to analyze metabolites released by human ILT (divided into luminal and abluminal layers), aneurysm wall (AW), and healthy wall (HW). Statistical analysis was used to compare luminal with abluminal ILT layer, ILT with AW, and AW with HW to select the metabolites exchanged between tissue and external medium. Identified compounds are related to inflammation and oxidative stress and indicate the possible role of fatty acid amides in AAA. Some metabolites (e.g., hippuric acid) had not been previously associated to aneurysm, others (fatty acid amides) have arisen, indicating a very promising line of research. 相似文献
53.
Michal Toborek rzej Malecki Rosario Garrido Mark P. Mattson Bernhard Hennig Byron Young 《Journal of neurochemistry》1999,73(2):684-692
Spinal cord trauma can cause a marked release of free fatty acids, in particular, arachidonic acid (AA), from cell membranes. Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study this hypothesis, cultured spinal cord neurons were exposed to increasing concentrations of AA (0.01-10 microM). AA-induced injury to spinal cord neurons was assessed by measurements of cellular oxidative stress, intracellular calcium levels, activation of nuclear factor-KB (NF-kappaB), and cell viability. AA treatment increased intracellular calcium concentrations and decreased cell viability. Oxidative stress increased significantly in neurons exposed to 1 and 10 microM AA. In addition, AA treatment activated NF-kappaB and decreased levels of the inhibitory subunit, IKB. It is interesting that manganese superoxide dismutase protein levels and levels of intracellular total glutathione increased in neurons exposed to this fatty acid for 24 h, consistent with a compensatory response to increased oxidative stress. These results strongly support the hypothesis that free fatty acids contribute to the tissue injury observed following spinal cord trauma. 相似文献
54.
Characterization of the C-terminal domain essential for toxic activity of adenylate cyclase toxin 总被引:1,自引:0,他引:1
Michal Bejerano Israel Nisan Albrecht Ludwig Werner Goebel & Emanuel Hanski 《Molecular microbiology》1999,31(1):381-392
Adenylate cyclase toxin (CyaA) of Bordetella pertussis belongs to the RTX family of toxins. These toxins are characterized by a series of glycine- and aspartate-rich nonapeptide repeats located at the C-terminal half of the toxin molecules. For activity, RTX toxins require Ca2+ , which is bound through the repeat region. Here, we identified a stretch of 15 amino acids (block A) that is located C-terminally to the repeat region and is essential for the toxic activity of CyaA. Block A is required for the insertion of CyaA into the plasma membranes of host cells. Mixing of a short polypeptide composed of block A and eight Ca2+ binding repeats with a mutant of CyaA lacking block A restores toxic activity fully. This in vitro interpolypeptide complementation is achieved only when block A is present together with the Ca2+ binding repeats on the same polypeptide. Neither a short polypeptide composed of block A only nor a polypeptide consisting of eight Ca2+ binding repeats, or a mixture of these two polypeptides, complement toxic activity. It is suggested that functional complementation occurs because of binding between the Ca2+ binding repeats of the short C-terminal polypeptide and the Ca2+ binding repeats of the CyaA mutant lacking block A. 相似文献
55.
An integrated UASB-sludge digester system for raw domestic wastewater treatment in temperate climates 总被引:1,自引:0,他引:1
To improve the performance of an upflow anaerobic sludge blanket (UASB) reactor treating raw domestic wastewater under temperate climates conditions, the addition of a sludge digester to the process was investigated. With the decrease in temperature, the COD removal decreased from 78% at 28 °C to 42% at 10 °C for the UASB reactor operating alone at a hydraulic retention time of 6 h. The decrease was attributed to low hydrolytic activity at lower temperatures that reduced suspended matter degradation and resulted in solids accumulation in the top of the sludge blanket. Solids removed from the upper part of the UASB sludge were treated in an anaerobic digester. Based on sludge degradation kinetics at 30 °C, a digester of 0.66 l per liter of UASB reactor was design operating at a 3.20 days retention time. Methane produced by the sludge digester is sufficient to maintain the temperature at 30 °C. 相似文献
56.
Michal Jarnik Jiang-Qing Tang Maria Korab-Laskowska Ewa Zie
tkiewicz Guy Cardinal Izabella Gorska-Flipot Daniel Sinnett Damian Labuda 《Genomics》1996,36(3):388
We studied two systems of multilocus markers revealed by PCR using primers directing amplification betweenAlurepeats in a tail-to-tail orientation. Genomic polymorphisms were detected as the presence or absence of the electrophoretic bands representing DNA fragments of a given length. A total of 104 such fragments segregating as Mendelian markers in a panel of eight CEPH families were analyzed by two-point linkage analysis. Fifty-one of these fragments were localized with respect to CEPH markers; they represented 33 loci, 7 of which were multiallelic. Locus-specific oligonucleotides were developed and used as hybridization probes to identify the mapped loci within a complex pattern of inter-AluPCR products. A great proportion of inter-AluPCR polymorphisms represented length variants within amplified DNA segments, while others were presumably due to mutations within the priming sites. To describe the expected number of informative loci per typing experiment we introduced a parameter called overall informativity (OI), which provides a single measure of the multiplex ratio and the informativity of markers contributing to a multilocus system (OIof a single locus is equivalent to its heterozygosity and cannot exceed 0.5 for a biallelic codominant marker). HighOIvalues (5.8 and 11.5) of the two presented systems of inter-AluPCR markers of random chromosomal distribution render them suitable for mapping genomic rearrangements such as genomic deletions in tumoral tissues. This was illustrated by the detection of loss of heterozygosity in the 9q22–qter region in sporadic colon cancer. 相似文献
57.
Summary Microstratigraphic, sedimentological, and taphonomic features of the Ferraz Shell Bed, from the Upper Permian (Kazanian-Tatarian?)
Corumbataí Formation of Rio Claro Region (the Paraná Basin, Brazil), indicate that the bed consists of four distinct microstratigraphic
units. They include, from bottom to top, a lag concentration (Unit 1), a partly reworked storm deposit (Unit 2), a rapidly
deposited sandstone unit with three thin horizons recording episodes of reworking (Unit 3), and a shell-rich horizon generated
by reworking/winnowing that was subsequently buried by storm-induced obrution deposit (Unit 4). The bioclasts of the Ferraz
Shell Bed represent exclusively bivalve mollusks.Pinzonellaillusa andTerraia aequilateralis are the dominant species. Taphonomic analysis indicates that mollusks are heavily time-averaged (except for some parts of
Unit 3). Moreover, different species are time-averaged to a different degree (disharmonious time-averaging). The units differ
statistically from one another in their taxonomic and ecological composition, in their taphonomic pattern, and in the size-frequency
distributions of the two most common species. Other Permian shell beds of the Paraná Basin are simílar to the Ferraz Shell
Bed in their faunal composition (they typically contain similar sets of 5 to 10 bivalve species) and in their taphonomic,
sedimentologic, and microstratigraphic characteristics. However, rare shell beds that include 2–3 species only and are dominated
by articulated shells preserved in life position also occur. Diversity levels in the Permian benthic associations of the Paraná
Basin were very low, with the point diversity of 2–3 species and with the within-habitat and basin-wide (alpha and gamma)
diversities of 10 species, at most. The Paraná Basin benthic communities may have thus been analogous to low-diversity bivalve-dominated
associations of the present-day Baltic Sea. The ‘Ferraz-type’ shell beds of the Paraná Basin represent genetically complex
and highly heterogeneous sources of paleontological data. They are cumulative records of spectra of benthic ecosystems time-averaged
over long periods of time (102–104 years judging from actualistic research). Detailed biostratinomic reconstructions of shell beds can not only offer useful
insights into their depositional histories, but may also allow paleoecologists to optimize their sampling designs, and consequently,
refine paleoecological and paleoenvironmental interpretations. 相似文献
58.
Zehava Grossman Jonathan M. Schapiro Itzchak Levy Daniel Elbirt Michal Chowers Klaris Riesenberg Karen Olstein-Pops Eduardo Shahar Valery Istomin Ilan Asher Bat-Sheva Gottessman Yonat Shemer Hila Elinav Gamal Hassoun Shira Rosenberg Diana Averbuch Keren Machleb-Guri Zipi Kra-Oz Sara Radian-Sade Hagit Rudich Daniela Ram Shlomo Maayan Nancy Agmon-Levin Zev Sthoeger 《PloS one》2014,9(1)
Background
Analysis of potentially different impact of Lopinavir/Ritonavir (LPV/r) on non-B subtypes is confounded by dissimilarities in the conditions existing in different countries. We retrospectively compared its impact on populations infected with subtypes B and C in Israel, where patients infected with different subtypes receive the same treatment.Methods
Clinical and demographic data were reported by physicians. Resistance was tested after treatment failure. Statistical analyses were conducted using SPSS.Results
607 LPV/r treated patients (365 male) were included. 139 had HIV subtype B, 391 C, and 77 other subtypes. At study end 429 (71%) were receiving LPV/r. No significant differences in PI treatment history and in median viral-load (VL) at treatment initiation and termination existed between subtypes. MSM discontinued LPV/r more often than others even when the virologic outcome was good (p = 0.001). VL was below detection level in 81% of patients for whom LPV/r was first PI and in 67% when it was second (P = 0.001). Median VL decrease from baseline was 1.9±0.1 logs and was not significantly associated with subtype. Median CD4 increase was: 162 and 92cells/µl, respectively, for patients receiving LPV/r as first and second PI (P = 0.001), and 175 and 98, respectively, for subtypes B and C (P<0.001). Only 52 (22%) of 237 patients genotyped while under LPV/r were fully resistant to the drug; 12(5%) were partially resistant. In48%, population sequencing did not reveal resistance to any drug notwithstanding the virologic failure. No difference was found in the rates of resistance development between B and C (p = 0.16).Conclusions
Treatment with LPV/r appeared efficient and tolerable in both subtypes, B and C, but CD4 recovery was significantly better in virologically suppressed subtype-B patients. In both subtypes, LPV/r was more beneficial when given as first PI. Mostly, reasons other than resistance development caused discontinuation of treatment. 相似文献59.
60.