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991.
Michele Abate Karin Gravare Silbernagel Carl Siljeholm Angelo Di Iorio Daniele De Amicis Vincenzo Salini Suzanne Werner Roberto Paganelli 《Arthritis research & therapy》2009,11(3):235-15
The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the
prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be
considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are
expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators.
Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation.
It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of
tendinopathies. 相似文献
992.
Carl Hamsten Maja Neiman Jochen M. Schwenk Marica Hamsten John B. March Anja Persson 《Molecular & cellular proteomics : MCP》2009,8(11):2544-2554
A systematic approach to characterize the surface proteome of Mycoplasma mycoides subspecies mycoides small colony type (M. mycoides SC), the causative agent of contagious bovine pleuropneumonia (CBPP) in cattle, is presented. Humoral immune responses in 242 CBPP-affected cattle and controls were monitored against one-third of the surface proteins of M. mycoides SC in a high throughput magnetic bead-based assay. Initially, 64 surface proteins were selected from the genome sequence of M. mycoides SC and expressed as recombinant proteins in Escherichia coli. Binding of antibodies to each individual protein could then be analyzed simultaneously in minute sample volumes with the Luminex suspension array technology. The assay was optimized on Namibian CBPP-positive sera and Swedish negative controls to allow detection and 20-fold mean signal separation between CBPP-positive and -negative sera. Signals were proven to be protein-specific by inhibition experiments, and results agreed with Western blot experiments. The potential of the assay to monitor IgG, IgM, and IgA responses over time was shown in a proof-of-concept study with 116 sera from eight animals in a CBPP vaccine study. In conclusion, a toolbox with recombinant proteins and a flexible suspension array assay that allows multiplex analysis of humoral immune responses to M. mycoides SC has been created.Mycoplasma mycoides subsp. mycoides small colony type (M. mycoides SC)1 is the causative agent of contagious bovine pleuropneumonia (CBPP), a severe respiratory disease in cattle. It is a disease requiring official declaration to the World Organization for Animal Health (OIE) and that causes vast problems in Africa with severe socioeconomic consequences (1, 2). In 2006, 15 African countries reported 186 outbreaks of CBPP to the OIE. CBPP was eradicated from Europe in the beginning of the 20th century (3) but has reemerged in every decade since (4). Eradication was largely facilitated by slaughtering infected herds, which is still considered as the most efficient means of disease control and was successfully performed in Botswana in 1995 (5). However, this campaign was directly correlated to increased malnutrition in children (6) and is also considered to be too expensive for other African countries (2, 7). The use of chemotherapy in CBPP control is a debated subject, has long been discouraged, and is even illegal in some countries (1), mainly because of the risk of creating silent carriers of the disease (8). However, new antibiotics have shown positive effects (9), but extensive vaccinations are still considered the preferred option for prevention and control of CBPP in Africa (2, 10, 11). The vaccines currently in use are based on live attenuated M. mycoides SC strains and have several disadvantages such as short term immunity (12), poor protection as indicated in recent trials (4, 13), and even pathogenicity (13, 14).The two currently available tests for serological diagnosis of CBPP recommended by the OIE, the complement fixation test (15) and a competitive ELISA (16), are based on whole cell M. mycoides SC. For subcellular components of the organism, the genome sequence of M. mycoides SC strain PG1 (17) offers an emerging possibility to improve both diagnostic and therapeutic approaches with selected antigens. However, as for the 10 other Mycoplasma genomes sequenced, the genome sequences per se did not reveal any primary virulence factors common in other bacteria, such as adhesins or toxins (18). The few known molecular mechanisms of pathogenicity were recently reviewed (18) and include five lipoproteins studied in detail: LppA (19, 20), LppB (21), LppC (22) LppQ (23), and Vmm (24). Of these, LppQ has been used to develop an indirect ELISA (25), and Vmm, a variable surface protein, has recently been studied along with five novel putative variable surface proteins as recombinant proteins expressed in Escherichia coli (26). That study demonstrated the feasibility of producing recombinant surface proteins from M. mycoides SC in E. coli and screening for antibodies in sera from CBPP-affected bovines by Western and dot blotting.To explore further the immunogenicity of the M. mycoides SC surface proteome, a platform for multiplexed analysis of proteins using minute serum samples such as bead-based array systems (27) is desirable. One method is available from Luminex Corp. and uses spectrally distinguishable beads (28) to form an array in suspension. The array is analyzed in a flow cytometer-like instrument and can perform up to 100 simultaneous assays in a single reaction well. This platform has recently been used to determine binding specificities to antigens produced in a similar fashion (29) and to profile antibodies in serum toward six antigens of Mycobacterium tuberculosis (30).The aim of this study was to develop a rapid and highly multiplex method for affinity analysis of antibody levels in serum samples from CBPP-affected bovines against recombinant M. mycoides SC surface proteins. To facilitate this, a large set of surface proteins were cloned, expressed in E. coli, and purified. Furthermore, the bead-based assay conditions had to be optimized and verified for detection of immunoglobulin levels in bovine sera. This methodology would enable monitoring and protein-specific characterization of humoral immune responses during CBPP infections. As a secondary aim, the study was expanded to include specific IgG, IgA, and IgM responses in sera from a vaccine study with time series sampling from each animal over 8 months, covering prevaccination and 4 months postinfection. 相似文献
993.
Johan Lindgren Carl Alwmark Michael W. Caldwell Anthony R. Fiorillo 《Biology letters》2009,5(4):528-531
The physical nature of water and the environment it presents to an organism have long been recognized as important constraints on aquatic adaptation and evolution. Little is known about the dermal cover of mosasauroids (a group of secondarily aquatic reptiles that occupied a wide array of predatory niches in the Cretaceous marine ecosystems 92–65 Myr ago), a lack of information that has hindered inferences about the nature and level of their aquatic adaptations. A newly discovered Plotosaurus skeleton with integument preserved in three dimensions represents not only the first documented squamation in a mosasaurine mosasaur but also the first record of skin in an advanced member of the Mosasauroidea. The dermal cover comprises keeled and possibly osteoderm-reinforced scales that presumably contributed to an anterior–posterior channelling of the water flow and a reduction of microturbulent burst activities along the surface of the skin. Thus, hydrodynamic requirements of life in the water might have influenced the evolution of multiple-keeled body scales in advanced mosasauroids. 相似文献
994.
Liu J Desai KV Li Y Banu S Lee YK Qu D Heikkinen T Aaltonen K Muranen TA Kajiji TS Bonnard C Aittomäki K von Smitten K Blomqvist C Hopper JL Southey MC Brauch H;GENICA Consortium Chenevix-Trench G Beesley J Spurdle AB Chen X;Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer;Australian Ovarian Cancer Study Group Czene K Hall P Nevanlinna H Liu ET 《The HUGO journal》2009,3(1-4):31-40
995.
Objective
C-reactive protein (CRP) levels>3 mg/L and>10 mg/L are associated with high and very high cardiovascular risk, respectively, in the general population. Because rheumatoid arthritis (RA) confers excess cardiovascular mortality, we determined the prevalence of these CRP levels among RA patients stratified on the basis of their RA disease activity.Methods
We evaluated physician and patient global assessments of disease activity, tender and swollen 28 joint counts, erythrocyte sedimentation rate (ESR), and CRP measured in a single clinic visit for 151 RA patients. Disease activity was calculated using the Clinical Disease Activity Index (CDAI) and the Disease Activity Score 28 Joints (DAS28-ESR and DAS28-CRP).Results
Median CRP level was 5.3 mg/L. 68% of patients had CRP>3 mg/L, and 25% had CRP>10 mg/L. Of those with 0–1 swollen joints (n = 56), or 0–1 tender joints (n = 81), 64% and 67%, respectively, had CRP>3 mg/L, and 23% and 20%, respectively, had CRP>10 mg/L. Of those with remission or mildly active disease by CDAI (n = 58), DAS28-ESR (n = 39), or DAS28-CRP (n = 70), 49–66% had CRP>3 mg/L, and 10–14% had CRP>10 mg/L. Of patients with moderate disease activity by CDAI (n = 51), DAS28-ESR (n = 78), or DAS28-CRP (n = 66), 67–73% had CRP>3 mg/L, and 25–33% had CRP>10 mg/L.Conclusion
Even among RA patients whose disease is judged to be controlled by joint counts or standardized disease scores, a substantial proportion have CRP levels that are associated high or very high risk for future cardiovascular events in the general population. 相似文献996.
Efstathios Karathanasis Leslie Chan Lohitash Karumbaiah Kathleen McNeeley Carl J. D'Orsi Ananth V. Annapragada Ioannis Sechopoulos Ravi V. Bellamkonda 《PloS one》2009,4(6)
Background
Vascular endothelial growth factor (VEGF) receptor-2 is the major mediator of the mitogenic, angiogenic, and vascular hyperpermeability effects of VEGF on breast tumors. Overexpression of VEGF and VEGF receptor-2 is associated with the degree of pathomorphosis of the tumor tissue and unfavorable prognosis. In this study, we demonstrate that non-invasive quantification of the degree of tumor vascular permeability to a nanoprobe correlates with the VEGF and its receptor levels and tumor growth.Methodology/Principal Findings
We designed an imaging nanoprobe and a methodology to detect the intratumoral deposition of a 100 nm-scale nanoprobe using mammography allowing measurement of the tumor vascular permeability in a rat MAT B III breast tumor model. The tumor vascular permeability varied widely among the animals. Notably, the VEGF and VEGF receptor-2 gene expression of the tumors as measured by qRT-PCR displayed a strong correlation to the imaging-based measurements of vascular permeability to the 100 nm-scale nanoprobe. This is in good agreement with the fact that tumors with high angiogenic activity are expected to have more permeable blood vessels resulting in high intratumoral deposition of a nanoscale agent. In addition, we show that higher intratumoral deposition of the nanoprobe as imaged with mammography correlated to a faster tumor growth rate. This data suggest that vascular permeability scales to the tumor growth and that tumor vascular permeability can be a measure of underlying VEGF and VEGF receptor-2 expression in individual tumors.Conclusions/Significance
This is the first demonstration, to our knowledge, that quantitative imaging of tumor vascular permeability to a nanoprobe represents a form of a surrogate, functional biomarker of underlying molecular markers of angiogenesis. 相似文献997.
998.
Recent publications have described and applied a novel metric that quantifies the
genetic distance of an individual with respect to two population samples, and
have suggested that the metric makes it possible to infer the presence of an
individual of known genotype in a sample for which only the marginal allele
frequencies are known. However, the assumptions, limitations, and utility of
this metric remained incompletely characterized. Here we present empirical tests
of the method using publicly accessible genotypes, as well as analytical
investigations of the method''s strengths and limitations. The results
reveal that the null distribution is sensitive to the underlying assumptions,
making it difficult to accurately calibrate thresholds for classifying an
individual as a member of the population samples. As a result, the
false-positive rates obtained in practice are considerably higher than
previously believed. However, despite the metric''s inadequacies for
identifying the presence of an individual in a sample, our results suggest
potential avenues for future research on tuning this method to problems of
ancestry inference or disease prediction. By revealing both the strengths and
limitations of the proposed method, we hope to elucidate situations in which
this distance metric may be used in an appropriate manner. We also discuss the
implications of our findings in forensics applications and in the protection of
GWAS participant privacy. 相似文献
999.
Toby K McGovern William S Powell Brian J Day Carl W White Karuthapillai Govindaraju Harry Karmouty-Quintana Normand Lavoie Ju Jing Tan James G Martin 《Respiratory research》2010,11(1):138
Background
Exposure to chlorine (Cl2) causes airway injury, characterized by oxidative damage, an influx of inflammatory cells and airway hyperresponsiveness. We hypothesized that Cl2-induced airway injury may be attenuated by antioxidant treatment, even after the initial injury.Methods
Balb/C mice were exposed to Cl2 gas (100 ppm) for 5 mins, an exposure that was established to alter airway function with minimal histological disruption of the epithelium. Twenty-four hours after exposure to Cl2, airway responsiveness to aerosolized methacholine (MCh) was measured. Bronchoalveolar lavage (BAL) was performed to determine inflammatory cell profiles, total protein, and glutathione levels. Dimethylthiourea (DMTU;100 mg/kg) was administered one hour before or one hour following Cl2 exposure.Results
Mice exposed to Cl2 had airway hyperresponsiveness to MCh compared to control animals pre-treated and post-treated with DMTU. Total cell counts in BAL fluid were elevated by Cl2 exposure and were not affected by DMTU treatment. However, DMTU-treated mice had lower protein levels in the BAL than the Cl2-only treated animals. 4-Hydroxynonenal analysis showed that DMTU given pre- or post-Cl2 prevented lipid peroxidation in the lung. Following Cl2 exposure glutathione (GSH) was elevated immediately following exposure both in BAL cells and in fluid and this change was prevented by DMTU. GSSG was depleted in Cl2 exposed mice at later time points. However, the GSH/GSSG ratio remained high in chlorine exposed mice, an effect attenuated by DMTU.Conclusion
Our data show that the anti-oxidant DMTU is effective in attenuating Cl2 induced increase in airway responsiveness, inflammation and biomarkers of oxidative stress. 相似文献1000.
Mihalis I. Panayiotidis Rodrigo Franco Carl D. Bortner John A. Cidlowski 《Apoptosis : an international journal on programmed cell death》2010,15(7):834-849
Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic
volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The
Na+–K+-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function
have been suggested to be associated with apoptosis. We report here that the Na+–K+-ATPase inhibitor ouabain, potentiates apoptosis in the human lymphoma Jurkat cells exposed to Fas ligand (FasL) or tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL) but not other apoptotic agents such as H2O2, thapsigargin or UV-C implicating a role for the Na+–K+-ATPase in death receptor-induced apoptosis. Interestingly, ouabain also potentiated perturbations in cell Ca2+ homeostasis only in conjunction with the apoptotic inducer FasL but not TRAIL. Ouabain did not affect alterations in the
intracellular Ca2+ levels in response to H2O2, thapsigargin or UV-C. FasL-induced alterations in Ca2+ were not abolished in Ca2+-free medium but incubation of cells with BAPTA-AM inhibited both Ca2+ perturbations and the ouabain-induced potentiation of FasL-induced apoptosis. Our data suggest that the impairment of the
Na+–K+-ATPase activity during apoptosis is linked to perturbations in cell Ca2+ homeostasis that modulate apoptosis induced by the activation of Fas by FasL. 相似文献