全文获取类型
收费全文 | 420篇 |
免费 | 14篇 |
专业分类
434篇 |
出版年
2024年 | 2篇 |
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 13篇 |
2014年 | 20篇 |
2013年 | 23篇 |
2012年 | 30篇 |
2011年 | 23篇 |
2010年 | 27篇 |
2009年 | 16篇 |
2008年 | 25篇 |
2007年 | 19篇 |
2006年 | 19篇 |
2005年 | 6篇 |
2004年 | 18篇 |
2003年 | 10篇 |
2002年 | 9篇 |
2001年 | 9篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1992年 | 6篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1982年 | 3篇 |
1977年 | 2篇 |
1966年 | 2篇 |
1962年 | 2篇 |
1951年 | 4篇 |
1927年 | 2篇 |
1925年 | 2篇 |
1920年 | 2篇 |
1917年 | 2篇 |
1914年 | 2篇 |
1912年 | 3篇 |
1911年 | 7篇 |
1910年 | 2篇 |
1909年 | 4篇 |
1908年 | 5篇 |
1907年 | 3篇 |
1906年 | 4篇 |
1905年 | 3篇 |
排序方式: 共有434条查询结果,搜索用时 0 毫秒
1.
We report the case of a 59-year-old woman, investigated for disabling pain of the left thigh, unrelated to any traumatic event. Interrogation had found diffuse pain of myalgia-type and arthralgia-type for approximately a year without local inflammatory signs and insufficiency fractures of both calcaneus two years before. The Technetium 99m-labeled hydroxymethylene diphosphonate (99mTc-HDP) whole-body bone scintigraphy evidenced multiple hot spots on the higher third of left femur, rib cage, sternum, scapulae, pelvis, right hip and both calcaneus. Moreover, a more diffuse and heterogeneous prominent uptake appeared on rib cage, spine and pelvis. These images suggested a diffuse metastatic disease of the skeleton. The single photon emission computerized tomography guided by computerized tomography (SPECT/CT), centered on lumbar spine, pelvis and the upper end of femurs showed that the multiple hot spots were infact bone fractures. These findings pointed diagnosis to a metabolic disease. The clinical context was in favour of an osteomalacia. Further explorations showed an osteomalacia related to phosphate diabetes. A thorough work-up did not reveal any known aetiology. To date, idiopathic phosphate diabetes seems the most likely diagnosis. Nuclear medicine input in osteomalacia is discussed. 相似文献
2.
Annerieke C van Groenestijn Ingrid GL van de Port Carin D Schröder Marcel WM Post Hepke F Grupstra Esther T Kruitwagen Harmen van der Linde Reinout O van Vliet Margreet GH van de Weerd Leonard H van den Berg Eline Lindeman 《BMC neurology》2011,11(1):1-11
Background
Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain.Methods
We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles.Results
Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct.Conclusions
The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain. 相似文献3.
4.
Bélanger LF Roy S Tremblay M Brott B Steff AM Mourad W Hugo P Erikson R Charron J 《Molecular and cellular biology》2003,23(14):4778-4787
MEK is a dual-specificity kinase that activates the extracellular signal-regulated kinase (ERK) mitogen-activated protein (MAP) kinase upon agonist binding to receptors. The ERK/MAP kinase cascade is involved in cell fate determination in many organisms. In mammals, this pathway is proposed to regulate cell growth and differentiation. Genetic studies have shown that although a single Mek gene is present in Caenorhabditis elegans, Drosophila melanogaster, and Xenopus laevis, two Mek homologs, Mek1 and Mek2, are present in the mammalian cascade. The inactivation of the Mek1 gene leads to embryonic lethality and has revealed the unique role played by Mek1 during embryogenesis. To investigate the biological function of the second homolog, we have generated mice deficient in Mek2 function. Mek2 mutant mice are viable and fertile, and they do not present flagrant morphological alteration. Although several components of the ERK/MAP kinase cascade have been implicated in thymocyte development, no such involvement was observed for MEK2, which appears to be nonessential for thymocyte differentiation and T-cell-receptor-induced proliferation and apoptosis. Altogether, our findings demonstrate that MEK2 is not necessary for the normal development of the embryo and T-cell lineages, suggesting that the loss of MEK2 can be compensated for by MEK1. 相似文献
5.
Larkin JL Gabriel M Gerhold RW Yabsley MJ Wester JC Humphreys JG Beckstead R Dubey JP 《The Journal of parasitology》2011,97(3):425-429
Understanding the role of disease in population regulation is important to the conservation of wildlife. We evaluated the prevalence of Toxoplasma gondii exposure and Sarcocystis spp. infection in 46 road-killed and accidentally trapper-killed fisher (Martes pennanti) carcasses collected and stored at -20 C by the Pennsylvania Game Commission from February 2002 to October 2008. Blood samples were assayed for T. gondii antibodies using the modified agglutination test (MAT, 1 : 25) and an indirect immunofluorescent antibody test (IFAT, 1 : 128). For genetic analysis, DNA samples were extracted from thoracic and pelvic limb skeletal muscle from each carcass to test for Sarcocystis spp. using 18s-rRNA PCR primers. Antibodies to T. gondii were found in 100% (38 of 38) of the fishers tested by MAT and in 71% (32 of 45) of the fishers tested by IFAT. PCR analysis revealed that 83% (38 of 46) of the fishers were positive for Sarcocystis spp. Sequence analysis of 7 randomly chosen amplicons revealed the fisher sarcocysts had a 98.3% to 99.1% identity to several avian Sarcocystis spp. sequences in GenBank. Data from our study suggest that a high percentage of fishers in Pennsylvania have been exposed to T. gondii and are infected with Sarcocystis spp. 相似文献
6.
Marion Millot Mourad Kaouadji Yves Champavier Aurélie Gamond Alain Simon Albert J. Chulia 《Phytochemistry letters》2013,6(1):31-35
In addition to known dibenzofuran derivatives such as (?)-usnic acid, (?)-isousnic acid and (?)-placodiolic acid, a Leprocaulon microscopicum acetone extract yielded a new compound, (±)-9-O-methylplacodiolic acid in a keto-enol equilibrium focused on the C-ring. Structures were established using mass spectrometry and combination of 1D and 2D NMR spectral data. 13C assignments of placodiolic acid were revised. Tautomers of the (±)-9-O-methylplacodiolic acid were only separated by GC and a thorough fragmentation study confirmed the structural features. To complete the study, evaluation of antiproliferative effects on HT-29 human colorectal cancer cells showed moderate activity for (?)-usnic acid only. 相似文献
7.
Abdenaceur Reghmit Farida Benzina-tihar Mourad Djeziri Rima Hadjouti Zahia Oukali Fatma Sahir-Halouane 《International microbiology》2022,25(4):817-829
International Microbiology - Trichoderma species have been widely recognized as biofertilizer fungi for their ability to produce phytohormones and enhance plant growth. In our current study,... 相似文献
8.
Beringue V Vilette D Mallinson G Archer F Kaisar M Tayebi M Jackson GS Clarke AR Laude H Collinge J Hawke S 《The Journal of biological chemistry》2004,279(38):39671-39676
Conversion of the cellular alpha-helical prion protein (PrP(C)) into a disease-associated isoform (PrP(Sc)) is central to the pathogenesis of prion diseases. Molecules targeting either normal or disease-associated isoforms may be of therapeutic interest, and the antibodies binding PrP(C) have been shown to inhibit prion accumulation in vitro. Here we investigate whether antibodies that additionally target disease-associated isoforms such as PrP(Sc) inhibit prion replication in ovine PrP-inducible scrapie-infected Rov cells. We conclude from these experiments that antibodies exclusively binding PrP(C) were relatively inefficient inhibitors of ScRov cell PrP(Sc) accumulation compared with antibodies that additionally targeted disease-associated PrP isoforms. Although the mechanism by which these monoclonal antibodies inhibit prion replication is unclear, some of the data suggest that antibodies might actively increase PrP(Sc) turnover. Thus antibodies that bind to both normal and disease-associated isoforms represent very promising anti-prion agents. 相似文献
9.
Yingying Lu Shichen Dong Baixia Hao Chang Li Kaiyuan Zhu Wenjing Guo Qian Wang King-Ho Cheung Connie WM Wong Wu-Tian Wu Huss Markus Jianbo Yue 《Autophagy》2014,10(11):1895-1905
Autophagy is a catabolic lysosomal degradation process essential for cellular homeostasis and cell survival. Dysfunctional autophagy has been associated with a wide range of human diseases, e.g., cancer and neurodegenerative diseases. A large number of small molecules that modulate autophagy have been widely used to dissect this process and some of them, e.g., chloroquine (CQ), might be ultimately applied to treat a variety of autophagy-associated human diseases. Here we found that vacuolin-1 potently and reversibly inhibited the fusion between autophagosomes and lysosomes in mammalian cells, thereby inducing the accumulation of autophagosomes. Interestingly, vacuolin-1 was less toxic but at least 10-fold more potent in inhibiting autophagy compared with CQ. Vacuolin-1 treatment also blocked the fusion between endosomes and lysosomes, resulting in a defect in general endosomal-lysosomal degradation. Treatment of cells with vacuolin-1 alkalinized lysosomal pH and decreased lysosomal Ca2+ content. Besides marginally inhibiting vacuolar ATPase activity, vacuolin-1 treatment markedly activated RAB5A GTPase activity. Expression of a dominant negative mutant of RAB5A or RAB5A knockdown significantly inhibited vacuolin-1-induced autophagosome-lysosome fusion blockage, whereas expression of a constitutive active form of RAB5A suppressed autophagosome-lysosome fusion. These data suggest that vacuolin-1 activates RAB5A to block autophagosome-lysosome fusion. Vacuolin-1 and its analogs present a novel class of drug that can potently and reversibly modulate autophagy. 相似文献
10.
We have analyzed a total of 12 different global and local multiple
protein-sequence alignment methods. The purpose of this study is to
evaluate each method's ability to correctly identify the ordered series of
motifs found among all members of a given protein family. Four
phylogenetically distributed sets of sequences from the hemoglobin, kinase,
aspartic acid protease, and ribonuclease H protein families were used to
test the methods. The performance of all 12 methods was affected by (1) the
number of sequences in the test sets, (2) the degree of similarity among
the sequences, and (3) the number of indels required to produce a multiple
alignment. Global methods generally performed better than local methods in
the detection of motif patterns.
相似文献