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991.
Taneja P Nasheuer HP Hartmann H Grosse F Fanning E Weisshart K 《The Biochemical journal》2007,407(2):313-320
The initiation of SV40 (simian virus 40) DNA replication requires the co-operative interactions between the viral Tag (large T-antigen), RPA (replication protein A) and Pol (DNA polymerase alpha-primase) on the template DNA. Binding interfaces mapped on these enzymes and expressed as peptides competed with the mutual interactions of the native proteins. Prevention of the genuine interactions was accomplished only prior to the primer synthesis step and blocked the assembly of a productive initiation complex. Once the complex was engaged in the synthesis of an RNA primer and its extension, the interfering effects of the peptides ceased, suggesting a stable association of the replication factors during the initiation phase. Specific antibodies were still able to disrupt preformed interactions and inhibited primer synthesis and extension activities, underlining the crucial role of specific protein-protein contacts during the entire initiation process. 相似文献
992.
993.
994.
Kurth I Thompson DA Rüther K Feathers KL Chrispell JD Schroth J McHenry CL Schweizer M Skosyrski S Gal A Hübner CA 《Molecular and cellular biology》2007,27(4):1370-1379
RDH12 codes for a member of the family of short-chain alcohol dehydrogenases/reductases proposed to function in the visual cycle that supplies the chromophore 11-cis retinal to photoreceptor cells. Mutations in RDH12 cause severe and progressive childhood onset autosomal-recessive retinal dystrophy, including Leber congenital amaurosis. We generated Rdh12 knockout mice, which exhibited grossly normal retinal histology at 10 months of age. Levels of all-trans and 11-cis retinoids in dark- and light-adapted animals and scotopic and photopic electroretinogram (ERG) responses were similar to those for the wild type, as was recovery of the ERG response following bleaching, for animals matched for an Rpe65 polymorphism (p.L450M). Lipid peroxidation products and other measures of oxidative stress did not appear to be elevated in Rdh12(-/-) animals. RDH12 was localized to photoreceptor inner segments and the outer nuclear layer in both mouse and human retinas by immunohistochemistry. The present findings, together with those of earlier studies showing only minor functional deficits in mice deficient for Rdh5, Rdh8, or Rdh11, suggest that the activity of any one isoform is not rate limiting in the visual response. 相似文献
995.
Fortschegger K Wagner B Voglauer R Katinger H Sibilia M Grillari J 《Molecular and cellular biology》2007,27(8):3123-3130
SNEV (Prp19, Pso4, NMP200) is a nuclear matrix protein known to be involved in pre-mRNA splicing, ubiquitylation, and DNA repair. In human umbilical vein endothelial cells, SNEV overexpression delayed the onset of replicative senescence. Here we analyzed the function of the mouse SNEV gene in vivo by employing homologous recombination in mice and conclude that SNEV is indispensable for early mouse development. Mutant preimplantation embryos initiated blastocyst formation but died shortly thereafter. Outgrowth of SNEV-null blastocysts showed a lack of proliferation of cells of the inner cell mass, which subsequently underwent cell death. While SNEV-heterozygous mice showed no overt phenotype, heterozygous mouse embryonic fibroblast cell lines with reduced SNEV levels displayed a decreased proliferative potential in vitro. Our experiments demonstrate that the SNEV protein is essential, functionally nonredundant, and indispensable for mouse development. 相似文献
996.
Sandoval A Arikkath J Monjaraz E Campbell KP Felix R 《Cellular and molecular neurobiology》2007,27(7):901-908
(1) Voltage-gated Ca2+ (CaV) channels are multi-subunit membrane complexes that allow depolarization-induced Ca2+ influx into cells. The skeletal muscle L-type CaV channels consist of an ion-conducting CaV1.1 subunit and auxiliary α2δ−1, β1 and γ1 subunits. This complex serves both as a CaV channel and as a voltage sensor for excitation–contraction coupling. (2) Though much is known about the mechanisms by which
the α2δ−1 and β1 subunits regulate CaV channel function, there is far less information on the γ1 subunit. Previously, we characterized the interaction of γ1 with the other components of the skeletal CaV channel complex, and showed that heterologous expression of this auxiliary subunit decreases Ca2+ current density in myotubes from γ1 null mice. (3) In the current report, using Western blotting we show that the expression of the CaV1.1 protein is significantly lower when it is heterologously co-expressed with γ1. Consistent with this, patch-clamp recordings showed that transient transfection of γ1 drastically inhibited macroscopic currents through recombinant N-type (CaV2.2/α2δ−1/β3) channels expressed in HEK-293 cells. (4) These findings provide evidence that co-expression of the auxiliary γ1 subunit results in a decreased expression of the ion-conducting subunit, which may help to explain the reduction in Ca2+ current density following γ1 transfection. 相似文献
997.
Christesen HB Brusgaard K Alm J Sjöblad S Hussain K Fenger C Rasmussen L Hovendal C Otonkoski T Jacobsen BB 《Hormone research》2007,67(4):184-188
BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations. 相似文献
998.
Breast-fed preterm infants often show a better outcome, partly ascribed to the benefit of insulin-like growth factors (IGFs) and their binding proteins (IGFBP). We compared IGF-I, IGF-II, IGFBP-2 and IGFBP-3 levels, measured by radioimmunoassays in milk samples from 30 mothers of preterm (<31 weeks) and from 19 mothers of term (>37 weeks) infants at days 7 and 21 postpartum. Proteolysis of IGFBP-2 within mother's milk and digestion of (125)I-IGF-II and (125)I-IGFBP-2 by gastric juice from neonates were assessed by electrophoretic techniques. Mean concentrations did not differ between preterm and term milk: IGF-I (2.8 +/- 0.2 vs. 2.3 +/- 0.1 ng/ml), IGF-II (12.0 +/- 0.4 vs. 12.2 +/- 0.5 ng/ml), IGFBP-3 (100.0 +/- 5.1 vs. 80.0 +/- 5.8 ng/ml), but did so for IGFBP-2 (3,144 +/- 172 vs. 2,428 +/- 188 ng/ml, p < 0.02). Immunoblots revealed 42% (p < 0.05) more IGFBP-2 fragments of 14 and 25 kDa in preterm milk. Incubation with gastric juice caused cleavage of (125)I-IGFBP-2 and partial cleavage of (125)I-IGF-II. Mutual complexation protected IGF-II and IGFBP-2 from cleavage, suggesting that both are likely to arrive in the bowel in an intact form to exert promotive effects. The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants. 相似文献
999.
Müller WE Eckert C Kropf K Wang X Schlossmacher U Seckert C Wolf SE Tremel W Schröder HC 《Cell and tissue research》2007,329(2):363-378
The siliceous sponge Monorhaphis chuni (Hexactinellida) synthesizes the largest biosilica structures on earth (3 m). Scanning electron microscopy has shown that
these spicules are regularly composed of concentrically arranged lamellae (width: 3–10 μm). Between 400 and 600 lamellae have
been counted in one giant basal spicule. An axial canal (diameter: ~2 μm) is located in the center of the spicules; it harbors
the axial filament and is surrounded by an axial cylinder (100–150 μm) of electron-dense homogeneous silica. During dissolution
of the spicules with hydrofluoric acid, the axial filament is first released followed by the release of a proteinaceous tubule.
Two major proteins (150 kDa and 35 kDa) have been visualized, together with a 24-kDa protein that cross-reacts with antibodies
against silicatein. The spicules are surrounded by a collagen net, and the existence of a hexactinellidan collagen gene has
been demonstrated by cloning it from Aphrocallistes vastus. During the axial growth of the spicules, silicatein or the silicatein-related protein is proposed to become associated with
the surface of the spicules and to be finally internalized through the apical opening to associate with the axial filament.
Based on the data gathered here, we suggest that, in the Hexactinellida, the growth of the spicules is mediated by silicatein
or by a silicatein-related protein, with the orientation of biosilica deposition being controlled by lectin and collagen.
Carsten Eckert was previously with the Museum für Naturkunde, Invalidenstrasse 43, 10115 Berlin, Germany.
The collagen sequence from Aphrocallistes vastus reported here, viz., [COL_APHRO] APHVACOL (accession number AM411124), has been deposited in the EMBL/GenBank data base.
This work was supported by grants from the European Commission, the Deutsche Forschungsgemeinschaft, the Bundesministerium
für Bildung und Forschung Germany (project: Center of Excellence BIOTECmarin), the National Natural Science Foundation of China (grant no. 50402023), and the International Human Frontier Science
Program. 相似文献
1000.
Döring B Pfitzer G Adam B Liebregts T Eckardt D Holtmann G Hofmann F Feil S Feil R Willecke K 《Cell and tissue research》2007,327(2):333-342
Connexin43 (Cx43) gap-junction channels are highly abundant in intestinal smooth muscle but their functional impact has not
been studied so far. Here, we have aimed to elucidate the functional role of Cx43 in the tunica muscularis of the mouse intestine
in vivo. Transgenic mice with conditional deletion of Cx43 in smooth muscle cells (SMC) were generated. Histological investigations
by immunofluorescence analyses and organ-bath recordings to assess the contractility of intestinal tissue strips were carried
out. Measurements of gastrointestinal transit and of the visceromotor response by utilizing a standardized colorectal distension
model to quantify alterations of visceral sensory function were also performed in SMC-specific Cx43 null mice and control
littermates. Histologically, we found thickening of the tunica muscularis and a 13-fold increase of neutrophil infiltration
of the gastrointestinal wall of SMC-specific Cx43 null mice. These animals also exhibited a decrease of 29% in gastrointestinal
transit time. In contrast, the visceromotor response to a standardized colorectal distension was elevated, as was the contractility
in SMC-specific Cx43 null mice, compared with controls. Thus, SMC-specific ablation of Cx43 in mice leads to morphological
and functional alterations of the intestinal tunica muscularis, to gastrointestinal motor dysfunction and to altered visceral
sensory function.
This study was supported by a grant from the German Research Association (Wi 270/25-1,2) to K.W. and in part by the IFORES
program of the University Hospital, Essen, Germany. 相似文献