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171.
The collagen model peptide with sequence (Pro-Hyp-Gly)4-Pro-Gly-(Pro-Hyp-Gly)5 contains a central Gly-Pro-Gly interruption in the consensus collagen sequence. Its high-resolution crystal structure defines the molecular consequences of such an interruption for the collagen triple-helical conformation, and provides insight into possible structural and biological roles of similar interruptions in the -Gly-X-Y- repeating pattern found in non-fibrillar collagens. The peptide (denoted as the Hyp minus peptide or Hyp-) forms a rod-like triple helix structure without any bend or kink, and crystallizes in a quasi-hexagonal lattice. The two Pro-Hyp-Gly zones adopt the typical triple-helical collagen conformation with standard Rich and Crick II hydrogen bonding topology. Notably, the central zone containing the Gly-Pro-Gly interruption deviates from the standard structure in terms of hydrogen bonding topology, torsion angles, helical, and superhelical parameters. These deviations are highly localized, such that the standard features are regained within one to two residues on either side. Conformational variations and high temperature factors seen for the six chains of the asymmetric unit in the zone around the interruption point to the presence of a local region of considerable plasticity and flexibility embedded within two highly rigid and ordered standard triple-helical segments. The structure suggests a role for Gly-X-Gly interruptions as defining regions of flexibility and molecular recognition in the otherwise relatively uniform repeating collagen conformation. 相似文献
172.
The importance of micro mammals from many points of view, mainly with an ecological approach was stressed. The study of the spatial-temporal distribution of parasites in their hosts may be carried out in several ways. Tests done in collaboration with the Parasitology Laboratory in the Faculty of Chemistry at the University of Barcelona, the NRCS and the Department of Ecological Studies in Cosenza, have contributed to an understanding of the Helminth communities as relating to several intrinsic variables of microteriofauna as well as extrinsic ones, particularly those concerning environment, climate and season. These comparisons were made using statistical means which compared the categorical and dichotomic variables which would highlight risk differences and their effects on the system. Quantitative dependent variables were also considered in relation to the aforementioned qualitative variables. One of the models studied is that of logistic regression, which estimates the function of regression, connecting the probability of the presence of Helminth as a dependent variable, with biological and ecological parameters (independent variables) such as: gender, age, season of capture, bioclimate, biotope and trapping section. 相似文献
173.
Elena Riano Monica Martignoni Giuseppe Mancuso Daniele Cartelli† Francesca Crippa‡ Irene Toldo§ Gabriele Siciliano¶ Daniela Di Bella Franco Taroni Maria Teresa Bassi‡ Graziella Cappelletti† Elena I. Rugarli 《Journal of neurochemistry》2009,108(5):1277-1288
Hereditary spastic paraplegia (HSP) is characterized by weakness and spasticity of the lower limbs, owing to degeneration of corticospinal axons. The most common form is due to heterozygous mutations in the SPG4 gene, encoding spastin, a microtubule (MT)-severing protein. Here, we show that neurite growth in immortalized and primary neurons responds in pleiotropic ways to changes in spastin levels. Spastin depletion alters the development of primary hippocampal neurons leading to abnormal neuron morphology, dystrophic neurites, and axonal growth defects. By live imaging with End-Binding Protein 3-Fluorescent Green Protein (EB3-GFP), a MT plus-end tracking protein, we ascertained that the assembly rate of MTs is reduced when spastin is down-regulated. Spastin over-expression at high levels strongly suppresses neurite maintenance, while slight spastin up-regulation using an endogenous promoter enhances neurite branching and elongation. Spastin severing activity is exerted preferentially on stable acetylated and detyrosinated MTs. We further show that SPG4 nonsense or splice site mutations found in hereditary spastic paraplegia patients result in reduced spastin levels, supporting haploinsufficiency as the molecular cause of the disease. Our study reveals that SPG4 is a dosage-sensitive gene, and broadens the understanding of the role of spastin in neurite growth and MT dynamics. 相似文献
174.
Mitchell D Paniker L Sanchez G Bella Z Garaczi E Szell M Hamid Q Kemeny L Koreck A 《Journal of cellular and molecular medicine》2010,14(1-2):313-322
Ultraviolet radiation (UVR) phototherapy is a promising new treatment for inflammatory airway diseases. However, the potential carcinogenic risks associated with this treatment are not well understood. UV-specific DNA photoproducts were used as biomarkers to address this issue. Radioimmunoassay was used to quantify cyclobutane pyrimidine dimers (CPDs) and (6–4) photoproducts in DNA purified from two milieus: nasal mucosa samples from subjects exposed to intranasal phototherapy and human airway (EpiAirway™) and human skin (EpiDerm™) tissue models. Immunohistochemistry was used to detect CPD formation and persistence in human nasal biopsies and human tissue models. In subjects exposed to broadband ultraviolet radiation, DNA damage frequencies were determined prior to as well as immediately after treatment and at increasing times post-treatment. We observed significant levels of DNA damage immediately after treatment and efficient removal of the damage within a few days. No residual damage was observed in human subjects exposed to multiple UVB treatments several weeks after the last treatment. To better understand the molecular response of the nasal epithelium to DNA damage, parallel experiments were conducted in EpiAirway and EpiDerm model systems. Repair rates in these two tissues were very similar and comparable to that observed in human skin. The data suggest that the UV-induced DNA damage response of respiratory epithelia is very similar to that of the human epidermis and that nasal mucosa is able to efficiently repair UVB induced DNA damage. 相似文献
175.
Roberto Danovaro Joan Batista Company Cinzia Corinaldesi Gianfranco D'Onghia Bella Galil Cristina Gambi Andrew J. Gooday Nikolaos Lampadariou Gian Marco Luna Caterina Morigi Karine Olu Paraskevi Polymenakou Eva Ramirez-Llodra Anna Sabbatini Francesc Sardà Myriam Sibuet Anastasios Tselepides 《PloS one》2010,5(8)
Deep-sea ecosystems represent the largest biome of the global biosphere, but
knowledge of their biodiversity is still scant. The Mediterranean basin has been
proposed as a hot spot of terrestrial and coastal marine biodiversity but has
been supposed to be impoverished of deep-sea species richness. We summarized all
available information on benthic biodiversity (Prokaryotes, Foraminifera,
Meiofauna, Macrofauna, and Megafauna) in different deep-sea ecosystems of the
Mediterranean Sea (200 to more than 4,000 m depth), including open slopes, deep
basins, canyons, cold seeps, seamounts, deep-water corals and deep-hypersaline
anoxic basins and analyzed overall longitudinal and bathymetric patterns. We
show that in contrast to what was expected from the sharp decrease in organic
carbon fluxes and reduced faunal abundance, the deep-sea biodiversity of both
the eastern and the western basins of the Mediterranean Sea is similarly high.
All of the biodiversity components, except Bacteria and Archaea, displayed a
decreasing pattern with increasing water depth, but to a different extent for
each component. Unlike patterns observed for faunal abundance, highest negative
values of the slopes of the biodiversity patterns were observed for Meiofauna,
followed by Macrofauna and Megafauna. Comparison of the biodiversity associated
with open slopes, deep basins, canyons, and deep-water corals showed that the
deep basins were the least diverse. Rarefaction curves allowed us to estimate
the expected number of species for each benthic component in different
bathymetric ranges. A large fraction of exclusive species was associated with
each specific habitat or ecosystem. Thus, each deep-sea ecosystem contributes
significantly to overall biodiversity. From theoretical extrapolations we
estimate that the overall deep-sea Mediterranean biodiversity (excluding
prokaryotes) reaches approximately 2805 species of which about 66% is
still undiscovered. Among the biotic components investigated (Prokaryotes
excluded), most of the unknown species are within the phylum Nematoda, followed
by Foraminifera, but an important fraction of macrofaunal and megafaunal species
also remains unknown. Data reported here provide new insights into the patterns
of biodiversity in the deep-sea Mediterranean and new clues for future
investigations aimed at identifying the factors controlling and threatening
deep-sea biodiversity. 相似文献
176.
Jie Jack Li Veerabahu Shanmugasundaram Satya Reddy Laura L. Fleischer Zenquan Wang Yvonne Smith William G. Harter Wen-Song Yue Manju Swaroop Ling Li Christy Xiaodong Ji Danielle Dettling Bella Osak Laura R. Fitzgerald Robert Conradi 《Bioorganic & medicinal chemistry letters》2010,20(16):4932-4935
A series of aminomethylpyrazoles were prepared and evaluated using cell-based Smoothened β-lactamase reporter assay and Smoothened binding assay. Potent Smoothened antagonists 10k and 10l were found to inhibit hair growth in vivo in the C3H/HeN mouse hair growth model. The more selective compound 10l was tested negative in the 3T3 NRU assay, indicating a low risk for causing photo-irritation and was efficacious using the C3H/HeN mouse hair growth model although it was slightly less efficacious than that of the reference compound eflornithine (7). 相似文献
177.
Manrico Morroni Daniela Marzioni Michele Ragno Paolo Di Bella Elisabetta Cartechini Luigi Pianese Teresa Lorenzi Mario Castellucci Marina Scarpelli 《PloS one》2013,8(6)
Background and Purpose
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 gene mutations that result in vascular smooth muscle cell (VSMC) degeneration. Its distinctive feature by electron microscopy (EM) is granular osmiophilic material (GOM) detected in VSMC indentations and/or the extracellular space close to VSMCs. Reports of the sensitivity of EM in detecting GOM in biopsies from CADASIL patients are contradictory. We present data from 32 patients clinically suspected to have CADASIL and discuss the role of EM in its diagnosis in this retrospective study.Methods
Skin, skeletal muscle, kidney and pericardial biopsies were examined by EM; the NOTCH3 gene was screened for mutations. Skin and muscle biopsies from 12 patients without neurological symptoms served as controls.Results and Discussion
All GOM-positive patients exhibited NOTCH3 mutations and vice versa. This study i) confirms that EM is highly specific and sensitive for CADASIL diagnosis; ii) extends our knowledge of GOM distribution in tissues where it has never been described, e.g. pericardium; iii) documents a novel NOTCH3 mutation in exon 3; and iv) shows that EM analysis is critical to highlight the need for comprehensive NOTCH3 analysis. Our findings also confirm the genetic heterogeneity of CADASIL in a small Italian subpopulation and emphasize the difficulties in designing algorithms for molecular diagnosis. 相似文献178.
Carolin?Cornelius Angela?Trovato Salinaro Maria?Scuto Vincenzo?Fronte Maria?Teresa?Cambria Manuela?Pennisi Rita?Bella Pietro?Milone Antonio?Graziano Rosalia?Crupi Salvatore?Cuzzocrea Giovanni?Pennisi Vittorio?CalabreseEmail author 《Immunity & ageing : I & A》2013,10(1):41
Alzheimer’s Disease (AD) is a neurodegenerative disorder affecting up to one third of individuals reaching the age of 80. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed Vitagenes. Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs). In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects. Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders. 相似文献
179.
A. Capone S. Di Bella P. Chinello D. Chiappetta C. Campoli N. Petrosillo 《Mycopathologia》2013,175(3-4):361-363
Data guiding management of pulmonary mycetomas are based on uncontrolled trials and case reports. Surgical resection represents a definitive treatment associated with high mortality and sometimes not feasible due to clinical conditions. We report a case of an immunocompetent patient with multiple pulmonary mycetomas, suggestive for probable chronic aspergillosis, in which surgery was contraindicated. The patient experienced a good response to long-term oral voriconazole therapy with remarkable clinical and radiological improvement at three-month follow-up. In cases of probable chronic aspergillomas, when surgery is contraindicated, long-term antifungal therapy with voriconazole seems to be a valid alternative option. 相似文献
180.
Groisman B Shenkman M Ron E Lederkremer GZ 《The Journal of biological chemistry》2011,286(2):1292-1300
Although the trimming of α1,2-mannose residues from precursor N-linked oligosaccharides is an essential step in the delivery of misfolded glycoproteins to endoplasmic reticulum (ER)-associated degradation (ERAD), the exact role of this trimming is unclear. EDEM1 was initially suggested to bind N-glycans after mannose trimming, a role presently ascribed to the lectins OS9 and XTP3-B, because of their in vitro affinities for trimmed oligosaccharides. We have shown before that ER mannosidase I (ERManI) is required for the trimming and concentrates together with the ERAD substrate and ERAD machinery in the pericentriolar ER-derived quality control compartment (ERQC). Inhibition of mannose trimming prevents substrate accumulation in the ERQC. Here, we show that the mannosidase inhibitor kifunensine or ERManI knockdown do not affect binding of an ERAD substrate glycoprotein to EDEM1. In contrast, substrate association with XTP3-B and with the E3 ubiquitin ligases HRD1 and SCF(Fbs2) was inhibited. Consistently, whereas the ERAD substrate partially colocalized upon proteasomal inhibition with EDEM1, HRD1, and Fbs2 at the ERQC, colocalization was repressed by mannosidase inhibition in the case of the E3 ligases but not for EDEM1. Interestingly, association and colocalization of the substrate with Derlin-1 was independent of mannose trimming. The HRD1 adaptor protein SEL1L had been suggested to play a role in N-glycan-dependent substrate delivery to OS9 and XTP3-B. However, substrate association with XTP3-B was still dependent on mannose trimming upon SEL1L knockdown. Our results suggest that mannose trimming enables delivery of a substrate glycoprotein from EDEM1 to late ERAD steps through association with XTP3-B. 相似文献