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121.
The epithelial lining of the gastrointestinal (GI) tract is in a state of continuous cell renewal, and the proliferating and differentiating/differentiated cell populations are spatially clearly demarcated. Members of the epidermal growth factor (EGF) family of peptides, the trefoil peptides and enteroglucagon appear to be the most important enterotrophic molecules for both normal cell renewal and healing after cell damage. Transforming growth factor-a (TGF-a) appears to be the primary physiological ligand for the EGF receptor (EGFR), promoting normal cell renewal, and TGF-a/EGFR are part of an autocrine loop in many intestinal cancers. In response to damage, a differentiating cell lineage arises from adjacent epithelium secreting EGF, TGF-a and trefoil peptides; this may be viewed as part of a ‘repair kit’ in damaged endodermally-derived tissue. 相似文献
122.
Y. Li M. M. Bhargava A. Joseph L. Jin E. M. Rosen I. D. Goldberg 《In vitro cellular & developmental biology. Animal》1994,30(2):105-110
Summary Using an automated cell analyzer system, the effect of hepatocyte growth factor/scatter factor (HGF/SF), epidermal growth
factor (EGF), basic fibroblast growth factor (bFGF), endothelial acidic fibroblast growth factor (a-FGF), platelet derived
growth factor (PDGF), and recombinant human insulinlike growth factor (IGF) on the motility and morphology of Madin-Darby
canine kidney (MDCK), rat hepatomas, C2, and H5–6 and murine mammary carcinoma (EMT-6) cells was investigated. Treatment of MDCK cells with HGF/SF, bFGF, EGF, and a-FGF resulted
in an increase in average cell velocity and in the fraction of moving cells. Cells treated with the PDGF and IGF did not show
significant alterations in velocity. MDCK cells treated with each growth factor were classified into groups of “fast” and
“slow” moving cells based on their average velocities, and the average morphologic features of the two groups were quantitated.
Fast-moving cells had larger average area, circularity, and flatness as compared to slow-moving cells. Factors that stimulated
cell movement also induced alterations in cell morphologic parameters including spreading, flatness, area, and circularity.
HGF/SF also scattered and stimulated motility of C2 and H5–6 hepatoma cells. In contrast to MDCK cells, there was no significant difference between the morphology of the fast moving
and slow moving C2 and H5–6 cells. These studies suggest that growth factor cytokines have specific effects on motility of normal and tumor cells. 相似文献
123.
Synthesis of lipopolysaccharide O side chains by Pseudomonas aeruginosa PAO1 requires the enzyme phosphomannomutase. 总被引:11,自引:6,他引:5
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We have cloned a lipopolysaccharide (LPS) biosynthetic gene from Pseudomonas aeruginosa PAO1 that complements the defect in the production and incorporation of LPS O side chains in the LPS-rough strain AK1012. This gene was characterized by pulsed-field gel electrophoresis, deletion and restriction mapping of the cloned DNA, and biochemical analysis of the protein product. The cloned DNA was found to map to the 7-to-11-min region of the P. aeruginosa chromosome, and the gene needed for complementation of the LPS-rough phenotype was contained on a 2.6-kb HindIII-SacI fragment. This same size restriction fragment contains the alginate gene algC, which encodes the enzyme phosphomannomutase (PMM) and also maps to this region of the P. aeruginosa chromosome. The LPS-rough strain AK1012 was deficient in PMM activity, and this activity was restored to parental levels when the cloned gene was transferred to strain AK1012. In addition, the cloned gene could complement the PMM deficiency in the algC mutant strain 8858, and the cloned algC gene could restore the LPS-smooth phenotype to strain AK1012. These results indicate that the gene we have cloned is equivalent to the alginate gene algC. We designate this gene pmm to emphasize that it encodes the enzyme PMM, which has been shown to be essential for alginate production, and we demonstrate that PMM activity is required for the LPS-smooth phenotype in P. aeruginosa PAO1. 相似文献
124.
This communication describes a novel highly sensitive method for measuring the affinity of a monoclonal antibody for its antigen. It is based on a radioimmunoassay in which the antigen is labeled with radioactivity. It is therefore particularly well adapted to the study of trace amounts of radiolabeled polypeptide chains produced either in vivo, or in vitro by a cell free protein synthesis system or by chemical radiolabeling. It offers several advantages over previously described methods. Though making use of insolubilized antibody, it does measure the true affinity constant of the monoclonal antibody in solution for the antigen. It can be used even when the antigen is present at concentrations far below the dissociation constant of the antibody/antigen complex. It does not require the antigen or the antibody to be purified. In most cases, it requires no sophisticated equipment. This method could be easily adapted to the determination of the equilibrium constant of any type of protein/ligand system. 相似文献
125.
Nick S. Fradgley James Bacon Alison R. Bentley Germano Costa-Neto Andrew Cottrell Jose Crossa Jaime Cuevas Matthew Kerton Edward Pope Stéphanie M. Swarbreck Keith A. Gardner 《Global Change Biology》2023,29(5):1296-1313
Wheat is a major crop worldwide, mainly cultivated for human consumption and animal feed. Grain quality is paramount in determining its value and downstream use. While we know that climate change threatens global crop yields, a better understanding of impacts on wheat end-use quality is also critical. Combining quantitative genetics with climate model outputs, we investigated UK-wide trends in genotypic adaptation for wheat quality traits. In our approach, we augmented genomic prediction models with environmental characterisation of field trials to predict trait values and climate effects in historical field trial data between 2001 and 2020. Addition of environmental covariates, such as temperature and rainfall, successfully enabled prediction of genotype by environment interactions (G × E), and increased prediction accuracy of most traits for new genotypes in new year cross validation. We then extended predictions from these models to much larger numbers of simulated environments using climate scenarios projected under Representative Concentration Pathways 8.5 for 2050–2069. We found geographically varying climate change impacts on wheat quality due to contrasting associations between specific weather covariables and quality traits across the UK. Notably, negative impacts on quality traits were predicted in the East of the UK due to increased summer temperatures while the climate in the North and South-west may become more favourable with increased summer temperatures. Furthermore, by projecting 167,040 simulated future genotype–environment combinations, we found only limited potential for breeding to exploit predictable G × E to mitigate year-to-year environmental variability for most traits except Hagberg falling number. This suggests low adaptability of current UK wheat germplasm across future UK climates. More generally, approaches demonstrated here will be critical to enable adaptation of global crops to near-term climate change. 相似文献
126.
Alan M. Goldberg John M. Frazier David Brusick Michael S. Dickens Oliver Flint Stephen D. Gettings Richard N. Hill Robert L. Lipnick Kevin J. Renskers June A. Bradlaw Robert A. Scala Bellina Veronesi Sidney Green Neil L. Wilcox Rodger D. Curren 《In vitro cellular & developmental biology. Animal》1993,29(9):688-692
Summary The development and application of in vitro alternatives designed to reduce or replace the use of animals, or to lessen the
distress and discomfort of laboratory animals, is a rapidly developing trend in toxicology. However, at present there is no
formal administrative process to organize, coordinate, or evaluate validation activities. A framework capable of fostering
the validation of new methods is essential for the effective transfer of new technologic developments from the research laboratory
into practical use. This committee has identified four essential validation resources: chemical bank(s), cell and tissue banks,
a data bank, and reference laboratories. The creation of a Scientific Advisory Board composed of experts in the various aspects
and endpoints of toxicity testing, and representing the academic, industrial, and regulatory communities, is recommended.
Test validation acceptance is contingent on broad buy-in by disparate groups in the scientific community—academics, industry,
and government. This is best achieved by early and frequent communication among parties and agreement on common goals. It
is hoped that the creation of a validation infrastructure composed of the elements described in this report will facilitate
scientific acceptance and utilization of alternative methodologies and speed implementation of replacement, reduction, and
refinement alternatives in toxicity testing. 相似文献
127.
Alison Ke Evaristo Cedeño Jordan Karubian Luis Carrasco Fernando Castillo Nelson Gonzales Daniel S. Karp 《Biotropica》2023,55(5):1045-1057
Most studies comparing biodiversity between natural and human-modified landscapes focus on patterns in species occurrence or abundance, but do not consider how different habitat types meet species' breeding requirements. Organisms that use or nest in tree cavities may be especially threatened by habitat conversion due to the loss of their nesting sites. Although cavity-nesting bird diversity is highest in the tropics, little is known about how tropical birds use cavities, how agriculture affects their reproductive biology, and how effective nest boxes could be as a conservation strategy in tropical agriculture. Here, we explored how habitat conversion from tropical forests to pasture affects the abundance, nesting habitat availability, and nest success of cavity-nesting birds in Northwest Ecuador. We conducted bird surveys and measured natural cavity availability and use in forest and agriculture. We also added artificial nest boxes to forest and agriculture to see whether cavity limitation in agriculture would elicit higher use of artificial nest boxes. We found evidence of cavity limitation in agriculture—there were many more natural cavities in forest than in agriculture, as well as more avian use of nest boxes placed in agriculture as compared to forest. Our results suggest that it is important to retain remnant trees in tropical agriculture to provide critical nesting habitat for birds. In addition, adding nest boxes to tropical agricultural systems could be a good conservation strategy for certain species, including insectivores that could provide pest-control services to farmers. Abstract in Spanish is available with online material. 相似文献
128.
Mutations in paired-box-containing (Pax) genes have recently been found to be the primary lesions underlying human genetic disorders such as Waardenburg's Syndrome type 1 and mouse developmental mutants such as undulated (un), splotch (Sp), and small eye (Sey). In addition, PAX-6 is a strong candidate gene for aniridia in man. Eight independent Pax genes have been isolated in the mouse. All eight map to distinct regions of the mouse genome; they do not appear to be clustered in the same way as some groups of homeobox-containing genes. We have now mapped the human homologs of all eight of these genes; PAX genes are found on human Chromosomes (Chr) 1, 2, 7, 9, 10, 11, and 20. 相似文献
129.
Arpana Agrawal Sarah J. Brislin Kathleen K. Bucholz Danielle Dick Ronald P. Hart Emma C. Johnson Jacquelyn Meyers Jessica Salvatore Paul Slesinger COGA Collaborators Laura Almasy Tatiana Foroud Alison Goate Victor Hesselbrock John Kramer Samuel Kuperman Alison K. Merikangas John I. Nurnberger Jay Tischfield Howard J. Edenberg Bernice Porjesz 《Genes, Brain & Behavior》2023,22(5):e12864
130.
Roger S. McIntyre Mohammad Alsuwaidan Bernhard T. Baune Michael Berk Koen Demyttenaere Joseph F. Goldberg Philip Gorwood Roger Ho Siegfried Kasper Sidney H. Kennedy Josefina Ly-Uson Rodrigo B. Mansur R. Hamish McAllister-Williams James W. Murrough Charles B. Nemeroff Andrew A. Nierenberg Joshua D. Rosenblat Gerard Sanacora Alan F. Schatzberg Richard Shelton Stephen M. Stahl Madhukar H. Trivedi Eduard Vieta Maj Vinberg Nolan Williams Allan H. Young Mario Maj 《World psychiatry》2023,22(3):394-412
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. 相似文献