全文获取类型
收费全文 | 1624篇 |
免费 | 95篇 |
出版年
2023年 | 8篇 |
2022年 | 3篇 |
2021年 | 11篇 |
2020年 | 21篇 |
2019年 | 26篇 |
2018年 | 84篇 |
2017年 | 67篇 |
2016年 | 80篇 |
2015年 | 96篇 |
2014年 | 111篇 |
2013年 | 108篇 |
2012年 | 136篇 |
2011年 | 147篇 |
2010年 | 89篇 |
2009年 | 52篇 |
2008年 | 99篇 |
2007年 | 106篇 |
2006年 | 94篇 |
2005年 | 79篇 |
2004年 | 63篇 |
2003年 | 50篇 |
2002年 | 41篇 |
2001年 | 12篇 |
2000年 | 9篇 |
1999年 | 7篇 |
1998年 | 9篇 |
1997年 | 6篇 |
1995年 | 3篇 |
1993年 | 6篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1987年 | 7篇 |
1985年 | 6篇 |
1984年 | 6篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 5篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 2篇 |
1969年 | 2篇 |
1966年 | 2篇 |
1965年 | 2篇 |
1960年 | 3篇 |
1952年 | 2篇 |
排序方式: 共有1719条查询结果,搜索用时 15 毫秒
981.
Xiao Ming Wang Karine Soetaert Priska Peirs Micha?l Kalai Véronique Fontaine Jean Paul Dehaye Philippe Lefèvre 《PloS one》2015,10(4)
PknD is one of the eleven eukaryotic-like serine/threonine protein kinases (STPKs) of Mycobacterium tuberculosis (Mtb). In vitro phosphorylation assays with the active recombinant PknD showed that the intracellular protein NAD+-dependent malate dehydrogenase (MDH) is a substrate of this kinase. MDH, an energy-supplying enzyme, catalyzes the interconversion of malate and oxaloacetate and plays crucial roles in several metabolic pathways including the citric acid cycle. The phosphorylation site was identified on threonine residues and the phosphorylation inhibited the MDH activity. In vitro, the recombinant MDH could also be phosphorylated by at least five other STPKs, PknA, PknE, PknH, PknJ, and PknG. Immunoprecipitation analysis revealed that MDH was hyperphosphorylated in the bacteria at the beginning of the stationary and under oxygen-limited conditions by STPKs other than PknD. On the contrary, when PknD-deficient mutant mycobacteria were grown in a phosphate-depleted medium, MDH was not detectably phosphorylated. These results suggest that although the MDH is a substrate of several mycobacterial STPKs, the activity of these kinases can depend on the environment, as we identified PknD as a key element in the MDH phosphorylation assay under phosphate-poor conditions. 相似文献
982.
Background
Formation of compact and poorly lysable clots has been reported in thromboembolic disorders. Little is known about clot properties in bleeding disorders.Objectives
We hypothesized that more permeable and lysis-sensitive fibrin clots can be detected in women with heavy menstrual bleeding (HMB).Methods
We studied 52 women with HMB of unknown cause and 52 age-matched control women. Plasma clot permeability (Ks), turbidity and efficiency of fibrinolysis, together with coagulation factors, fibrinolysis proteins, and platelet aggregation were measured.Results
Women with HMB formed looser plasma fibrin clots (+16% [95%CI 7–18%] Ks) that displayed lower maximum absorbancy (-7% [95%CI -9 – -1%] ΔAbsmax), and shorter clot lysis time (-17% [95%CI -23 – -11%] CLT). The HMB patients and controls did not differ with regard to coagulation factors, fibrinogen, von Willebrand antigen, thrombin generation markers and the proportion of subjects with defective platelet aggregation. The patients had lower platelet count (-12% [95%CI -19 – -2%]), tissue plasminogen activator antigen (-39% [95%CI -41 – -29%] tPA:Ag), and plasminogen activator inhibitor-1 antigen (-28% [95%CI -38 – -18%] PAI-1:Ag) compared with the controls. Multiple regression analysis upon adjustment for age, body mass index, glucose, and fibrinogen showed that decreased tPA:Ag and shortened CLT were the independent predictors of HMB.Conclusions
Increased clot permeability and susceptibility to fibrinolysis are associated with HMB, suggesting that altered plasma fibrin clot properties might contribute to bleeding disorders of unknown origin. 相似文献983.
984.
Mariusz A. Bromke Jamal S. Sabir Fahad A. Alfassi Nahid H. Hajarah Saleh A. Kabli Abdulrahman L. Al-Malki Matt P. Ashworth Micha?l Méret Robert K. Jansen Lothar Willmitzer 《PloS one》2015,10(10)
Diatoms are very efficient in their use of available nutrients. Changes in nutrient availability influence the metabolism and the composition of the cell constituents. Since diatoms are valuable candidates to search for oil producing algae, measurements of diatom-produced compounds can be very useful for biotechnology. In order to explore the diversity of lipophilic compounds produced by diatoms, we describe the results from an analysis of 13 diatom strains. With the help of a lipidomics platform, which combines an UPLC separation with a high resolution/high mass accuracy mass spectrometer, we were able to measure and annotate 142 lipid species. Out of these, 32 were present in all 13 cultures. The annotated lipid features belong to six classes of glycerolipids. The data obtained from the measurements were used to create lipidomic profiles. The metabolomic overview of analysed cultures is amended by the measurement of 96 polar compounds. To further increase the lipid diversity and gain insight into metabolomic adaptation to nitrogen limitation, diatoms were cultured in media with high and low concentrations of nitrate. The growth in nitrogen-deplete or nitrogen-replete conditions affects metabolite accumulation but has no major influence on the species-specific metabolomic profile. Thus, the genetic component is stronger in determining metabolic patterns than nitrogen levels. Therefore, lipid profiling is powerful enough to be used as a molecular fingerprint for diatom cultures. Furthermore, an increase of triacylglycerol (TAG) accumulation was observed in low nitrogen samples, although this trend was not consistent across all 13 diatom strains. Overall, our results expand the current understanding of metabolomics diversity in diatoms and confirm their potential value for producing lipids for either bioenergy or as feed stock. 相似文献
985.
Objective
The aim of our study was to determine whether serum dehydroepiandrosterone sulphate (DHEAS) concentration and the models incorporating it could help clinicians to predict IVF outcomes in women with normal ovarian reserve undergoing their first long protocol.Study Design
We performed a retrospective analysis of 459 women undergoing cycles of intracytoplasmic sperm injection (ICSI) for the first time in a long GnRH agonist protocol.Results
Embryo transfer was performed in 407 women (88.7%). The fertilisation rate was 78.6%. The clinical pregnancy rate was 44.8% per started cycle and 50.6% per embryo transfer. Our univariate model revealed that the best predictors of clinical pregnancy were the number of mature oocytes, the number of embryos transferred and the number of good quality embryos, account for the clinical parameters that reflect ovarian reserve the best being AMH level and AFC. DHEAS did not predict clinical pregnancy (OR 1.001, 95% CI, 0.999–1.004). After adjusting for the number of embryos transferred and class of embryos in a multivariate model, the best predictors were age (OR 0.918, 95% CI, 0.867–0.972) and AFC (OR 1.022, 95% CI, 0.992–1.053). Serum DHEAS levels were positively correlated with AFC (r = 0.098, P<0.039) and testosterone levels (r = 0.371, P<0.001), as well as the number of mature oocytes (r = 0.109, P<0.019); serum DHEAS levels were negatively correlated with age (r = -0.220, P<0.001), follicle-stimulating hormone (FSH), (r = -0.116, P<0.015) and sex hormone-binding globulin (SHBG), (r = -0.193, P<0.001).Conclusions
DHEAS concentration (in addition to the known factors of ovarian reserve) does not predict clinical pregnancy in women with normal ovarian reserve who are undergoing ICSI. 相似文献986.
987.
988.
The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular
or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral
amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional
chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent
aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins
and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions
of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis
or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the
aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation
associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention. 相似文献
989.
Skrzypczak U Rutkiewicz E Pogorzelski A Witt M Zietkiewicz E 《Journal of applied genetics》2007,48(1):85-88
We screened a large group of primary ciliary dyskinesia/Kartagener syndrome (PCD/KS) patients and their siblings (148 patients from 126 unrelated families) for the presence of the CFTR mutations that are most frequently found in the Polish population: the severe F508del and 2,3del21kb, and the mild 3849+10kbC > T. No statistically significant increase in the frequency of these mutations was found in the studied group, as compared with the general population. This is consistent with an earlier observation in another population and indicates that the status of being a carrier of any of these CFTR mutations should not be considered as an important risk factor in PCD/KS pathogenesis. 相似文献
990.
Dwiecki K Górnas P Wilk A Nogala-Kałucka M Polewski K 《Cellular & molecular biology letters》2007,12(1):51-69
The effects of embedding up to 60 mol% of α-tocopherol (α-Toc) on the morphology and structure of the egg phosphatidylcholine
(PC) membrane were studied using spectroscopic techniques. The resulting vesicles were subjected to turbidometric and dynamic
light scattering measurements to evaluate their size distribution. The α-Toc intrinsic fluorescence and its quenching was
used to estimate the tocopherol position in the membrane. Optical microscopy was used to visualize morphological changes in
the vesicles during the inclusion of tocopherol into the 2 mg/ml PC membrane. The incorporation of up to 15 mol% of tocopherol
molecules into PC vesicles is accompanied by a linear increase in the fluorescence intensity and the simultaneous formation
of larger, multilamellar vesicles. Increasing the tocopherol concentration above 20 mol% induced structural and morphological
changes leading to the disappearance of micrometer-sized vesicles and the formation of small unilamellar vesicles of size
ranging from 30 to 120 nm, mixed micelles and non-lamellar structures. 相似文献