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151.
Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression 下载免费PDF全文
152.
Labarthe MC Halanek N Birchall L Russell N Desel C Todryk S Peters MJ Lucas A Falkenberg FW Dalgleish AG Whelan M Ward SJ 《Cancer immunology, immunotherapy : CII》2006,55(3):277-288
Allogeneic whole tumour cell vaccines are inherently practical compared with autologous vaccines. Cell lines are derived from
allogeneic tumour, grown in bulk and then administered as a vaccine to the patient, following irradiation, which not only
prevents any replication but also enhances antigen presentation. Protection is believed to occur through the presentation
of antigens shared between the syngeneic and allogeneic tumours. Although cytokine-transfected tumour whole cell vaccines
have been used clinically, little data is available comparing the effects of immunomodulatory cytokine-transfection directly
on the same cells when used as both an allogeneic and autologous vaccine. To address this, weakly immunogenic B16-F10 (H-2b) murine melanoma was transfected to secrete either GM-CSF, IL-4 or IL-7. Prophylactic vaccination of both syngeneic C57/BL6
(H-2b) (B6) and allogeneic C3H/Hej (H-2k) (C3H) mice showed the effects of transfected cytokine varied between models. Both GM-CSF and IL-7 significantly (P<0.05) increased the levels of protection within syngeneic B6 mice, but had a diminished effect (P>0.05) within C3H allogeneic mice. Allogeneic B16-F10 cells and syngeneic K1735 cells generated CTL against K1735 suggesting
cross-reactive immunity. Using cells labeled with fluorescent dye we demonstrate that irradiated vaccines, of either syngeneic
or allogeneic origin, appear to generate potent immune responses and fragments of either vaccine remain at the injection site
for up to 9 days. This study shows that protection can be enhanced in vivo by using transfected cytokine, but suggests that
irradiated whole cell vaccines, of either tissue-type, are rapidly processed. This leads to the conclusion that the cytokine
effects are transient and thus transfection with cytokine may be of limited long-term use in situ. 相似文献
153.
Consequences of Sphaeropsis tip blight disease for the phytohormone profile and antioxidative metabolism of its pine host 下载免费PDF全文
Bin Hu Hitoshi Sakakibara Mikiko Kojima Yumiko Takebayashi Johanna Bußkamp Gitta J. Langer Franziska S. Peters Jörg Schumacher Monika Eiblmeier Jürgen Kreuzwieser Heinz Rennenberg 《Plant, cell & environment》2018,41(4):737-754
Phytopathogenic fungi infections induce plant defence responses that mediate changes in metabolic and signalling processes with severe consequences for plant growth and development. Sphaeropsis tip blight, induced by the endophytic fungus Sphaeropsis sapinea that spreads from stem tissues to the needles, is the most widespread disease of conifer forests causing dramatic economic losses. However, metabolic consequences of this disease on bark and wood tissues of its host are largely unexplored. Here, we show that diseased host pines experience tissue dehydration in both bark and wood. Increased cytokinin and declined indole‐3‐acetic acid levels were observed in both tissues and increased jasmonic acid and abscisic acid levels exclusively in the wood. Increased lignin contents at the expense of holo‐cellulose with declined structural biomass of the wood reflect cell wall fortification by S. sapinea infection. These changes are consistent with H2O2 accumulation in the wood, required for lignin polymerization. Accumulation of H2O2 was associated with more oxidized redox states of glutathione and ascorbate pools. These findings indicate that S. sapinea affects both phytohormone signalling and the antioxidative defence system in stem tissues of its pine host during the infection process. 相似文献
154.
155.
156.
S.J. Lugowski D.C. Smith H. Bonek J. Lugowski W. Peters J. Semple 《Journal of trace elements in medicine and biology》2000,14(1):31-42
The increase, in the last two decades, in the application of silicones (polysiloxanes) and inorganic silicon compounds in medicine and the food industry, has exposed the human body to extensive contacts with these substances. Most silicone breast implants contain a gel consisting of a crosslinked silicone elastomer swollen by silicone oil (PDMS). Diffusion of PDMS through the silicone elastomer envelope and rupture of the envelope with release of the gel contents both occur clinically. The amount and distribution of silicone compounds in various tissues are key issues in the assessment of health problems connected with silicone implants. We have measured by GFAAS the Si content of tissues from normal and implant patients and the organic solvent extractable Si levels (assumed to be silicone), using careful control of sample collection and preparation. Whole blood levels were: implant patients mean 38.8 (SD 25.6) (microg/kg), controls mean 24.2 (SD 26.7) (microg/kg) in one study and subsequently 103.8 (SD 112.1) and 74.3 (SD 86.5) (microg/kg) in another study. Capsular tissue levels were: gel implants 25047 (SD 39313) (mg/kg of dry tissue), saline implants 20.0 (SD 27.3) (mg/kg of dry tissue) and controls 0.24 (SD 0.39) (mg/kg of dry tissue). Breast milk levels were: implant patients mean 58.7 (SD 33.8) (microg/kg), controls mean 51.1 (SD 31.0) (microg/kg); infant formula mean was 4.40 (mg/kg). Various precautions were undertaken to avoid Si contamination in this work, the most important being a) the use of a Class 100 laboratory for sample preparation and b) application of strict and elaborate washing procedure for specimen collection tools and laboratory plasticware. This data demonstrated that to properly interpret the importance of these numbers for human health, a larger study of "normal" levels of Si in human tissues should be undertaken and factors such as diet, water, race and geographical location should be considered. 相似文献
157.
Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea mutagenesis-driven forward genetics 下载免费PDF全文
Smits BM Peters TA Mul JD Croes HJ Fransen JA Beynon AJ Guryev V Plasterk RH Cuppen E 《Genetics》2005,170(4):1887-1896
The rat is the most extensively studied model organism and is broadly used in biomedical research. Current rat disease models are selected from existing strains and their number is thereby limited by the degree of naturally occurring variation or spontaneous mutations. We have used ENU mutagenesis to increase genetic variation in laboratory rats and identified a recessive mutant, named tornado, showing aberrant circling behavior, hyperactivity, and stereotypic head shaking. More detailed analysis revealed profound deafness due to disorganization and degeneration of the organ of Corti that already manifests at the onset of hearing. We set up a single nucleotide polymorphism (SNP)-based mapping strategy to identify the affected gene, revealing strong linkage to the central region of chromosome 1. Candidate gene resequencing identified a point mutation that introduces a premature stopcodon in Myo7a. Mutations in human MYO7A result in Usher syndrome type 1B, a severe autosomal inherited recessive disease that involves deafness and vestibular dysfunction. Here, we present the first characterized rat model for this disease. In addition, we demonstrate proof of principle for the generation and cloning of human disease models in rat using ENU mutagenesis, providing good perspectives for systematic phenotypic screens in the rat. 相似文献
158.
Tsipouri V Curtin JA Nolan PM Vizor L Parsons CA Clapham CM Latham ID Rooke LJ Martin JE Peters J Hunter AJ Rogers D Rastan S Brown SD Fisher EM Spurr NK Gray IC 《Comparative and Functional Genomics》2004,5(2):123-127
Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1Mit214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximalMmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes. 相似文献
159.
Peters JU Weber S Kritter S Weiss P Wallier A Boehringer M Hennig M Kuhn B Loeffler BM 《Bioorganic & medicinal chemistry letters》2004,14(6):1491-1493
The influence of aromatic substitution on a newly discovered class of inhibitors of dipeptidyl peptidase IV was investigated. A 10(5)-fold increase in potency was achieved by the optimization of aromatic substituents in a parallel chemistry program. The observed SAR could be explained by an X-ray structure of the protein-ligand complex. 相似文献
160.
Blume A Angulo J Biet T Peters H Benie AJ Palcic M Peters T 《The Journal of biological chemistry》2006,281(43):32728-32740
Saturation transfer difference NMR experiments on human blood group B alpha-(1,3)-galactosyltransferase (GTB) for the first time provide a comprehensive set of binding epitopes of donor substrate analogs in relation to the natural donor UDP-Gal. This study revealed that the enzyme binds several UDP-activated sugars, including UDP-Glc, UDP-GlcNAc, and UDP-GalNAc. In all cases, UDP is the dominant binding epitope. To identify the minimum requirements for specific binding, a detailed analysis utilizing a fragment-based approach was employed. The binding of donor substrate to GTB is essentially controlled by the base as a "molecular anchor." Uracil represents the smallest fragment that is recognized, whereas CDP, AMP, and GDP do not exhibit any significant binding affinity for the enzyme. The ribose and beta-phosphate moieties increase the affinity of the ligands, whereas the pyranose sugar apparently weakens the binding, although this part of the molecule controls the specificity of the enzyme. Accordingly, UDP represents the best binder. The binding affinities of UDP-Gal, UDP-Glc, and UMP are about the same, but lower than that of UDP. Furthermore, we observed that beta-D-galactose and alpha-D-galactose bind weakly to GTB. Whereas beta-D-galactose binds to the acceptor and donor sites, it is suggested that alpha-D-galactose occupies a third hitherto unknown binding pocket. Finally, our experiments revealed that modulation of enzymatic activity by metal ions critically depends on the total enzyme concentration, raising the question as to which of the bivalent metal cations Mg(2+) and Mn(2+) is more relevant under physiological conditions. 相似文献