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51.
Kousei Ohshima Masaki Mogi Fei Jing Jun Iwanami Kana Tsukuda Li-Juan Min Akiyoshi Ogimoto Bj?rn Dahl?f Ulrike M. Steckelings Tomas Unger Jitsuo Higaki Masatsugu Horiuchi 《PloS one》2012,7(11)
Objectives
The role of angiotensin II type 2 (AT2) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue.Methods
T2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21 and/or a PPARγ antagonist, GW9662 in drinking water for 2 weeks. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[3H] deoxy-D-glucose in white adipose tissue. Morphological changes of adipose tissues as well as adipocyte differentiation and inflammatory response were examined.Results
Treatment with C21 ameliorated insulin resistance in KK-Ay mice without influencing blood pressure, at least partially through effects on the PPARγ pathway. C21 treatment increased serum adiponectin concentration and decreased TNF-α concentration; however, these effects were attenuated by PPARγ blockade by co-treatment with GW9662. Moreover, we observed that administration of C21 enhanced adipocyte differentiation and PPARγ DNA-binding activity, with a decrease in inflammation in white adipose tissue, whereas these effects of C21 were attenuated by co-treatment with GW9662. We also observed that administration of C21 restored β cell damage in diabetic pancreatic tissue.Conclusion
The present study demonstrated that direct AT2 receptor stimulation by C21 accompanied with PPARγ activation ameliorated insulin resistance in T2DM mice, at least partially due to improvement of adipocyte dysfunction and protection of pancreatic β cells. 相似文献52.
Nevoigt E Pilger R Mast-Gerlach E Schmidt U Freihammer S Eschenbrenner M Garbe L Stahl U 《FEMS yeast research》2002,2(2):225-232
The GPD1 gene encoding the glycerol-3-phosphate dehydrogenase was overexpressed in an industrial lager brewing yeast (Saccharomyces cerevisiae ssp. carlsbergensis) to reduce the content of ethanol in beer. The amount of glycerol produced by the GPD1-overexpressing yeast in fermentation experiments simulating brewing conditions was increased 5.6 times and ethanol was decreased by 18% when compared to the wild-type. Overexpression of GPD1 does not affect the consumption of wort sugars. Only minor changes in the concentration of higher alcohols, esters and fatty acids could be observed in beer produced by the GPD1-overexpressing brewing yeast. However, the concentrations of several other by-products, particularly acetoin, diacetyl and acetaldehyde, were considerably increased. 相似文献
53.
Just W Baumstark A Hameister H Schreiner B Reisert I Hakhverdyan M Vogel W 《Cytogenetic and genome research》2002,96(1-4):146-153
Mammalian sex determination and gonad differentiation are the result of a complex interaction of fine-tuned spatial and temporal gene expression with threshold levels of individual genes. The male pathway is initiated by SRY. Some exceptional mammals determine male sex without the SRY gene and even without a Y chromosome. Ellobius lutescens in this report is one example of this "weird" species. We provide key data on the genomic level that there are no coarse differences in the genomes of male and female animals by comparative genomic hybridization. On the gene level we studied the gene Nr5a1 for the orphan nuclear receptor, steroidogenic factor SF-1, a central constituent for gonad differentiation and adrenal gland development. The Ellobius lutescens Nr5a1 gene was mapped to the proximal short arm of chromosome 2 by fluorescence in situ hybridization. In addition, we provide evidence by linkage analysis in two E. lutescens pedigrees that Nr5a1 is not the key male sex-determining gene in Ellobius lutescens. 相似文献
54.
Miguel A. Lanaspa Laura G. Sanchez-Lozada Christina Cicerchi Nanxing Li Carlos A. Roncal-Jimenez Takuji Ishimoto Myphuong Le Gabriela E. Garcia Jeffrey B. Thomas Christopher J. Rivard Ana Andres-Hernando Brandi Hunter George Schreiner Bernardo Rodriguez-Iturbe Yuri Y. Sautin Richard J. Johnson 《PloS one》2012,7(10)
55.
The gravitational work of breathing was determined by measuring the vertical motion of body mass. The subject, seated or lying supine on a force platform, performed breathing maneuvers in which rib cage volume (Vrc) and abdominal volume (Vab) were changed in varying proportions. The increment in the vertical force exerted on the platform and Vrc and Vab were measured over the course of each maneuver. The force signal was integrated twice with respect to time to obtain the change in the product of mass and height of the subject. This was multiplied by the gravitational acceleration to obtain the change in the gravitational potential (Ug). Simultaneous values of Ug, Vrc, and Vab were taken from the data, and the values of the coefficients for which the following equation best fit these values were determined: Ug = a1 Vrc + a2 Vab + (1/2)a11 Vrc2 + a12 Vrc Vab + (1/2)a22 Vab2. The coefficients a1 and a2 can be interpreted as the values of the expiratory gravitational forces on the rib cage and abdomen, respectively. In the seated posture, the force on the rib cage is expiratory and the force on the abdomen is inspiratory; the magnitudes of both are approximately 8 cmH2O. In the supine posture, both are expiratory forces of approximately 9 cmH2O. The coefficients of the quadratic terms in Ug are all positive, and the gravitational work per unit volume of chest wall expansion increases with increasing volume in both postures. The coefficients of the quadratic terms can be interpreted as gravitational contributions to the elastances of the compartments. 相似文献
56.
Purification and Properties of a Thermoactive Glucoamylase from Clostridium thermosaccharolyticum 下载免费PDF全文
A bacterial glucoamylase was purified from the anaerobic thermophilic bacterium Clostridium thermosaccharolyticum and characterized. The enzyme, which was purified 63-fold, with a yield of 36%, consisted of a single subunit with an apparent molecular mass of 75 kDa. The purified enzyme was able to attack α-1,4- and α-1,6-glycosidic linkages in various α-glucans, liberating glucose with a β-anomeric configuration. The purified glucoamylase, which was optimally active at 70°C and pH 5.0, attacked preferentially polysaccharides such as starch, glycogen, amylopectin, and maltodextrin. The velocity of oligosaccharide hydrolysis decreased with a decrease in the size of the substrate. The Km values for starch and maltose were 18 mg/ml and 20 mM, respectively. Enzyme activity was not significantly influenced by Ca2+, EDTA, or α- or β-cyclodextrins. 相似文献
57.
Arby Abtin Pavol Kudela Ulrike Beate Mayr Michael Mildner Werner Lubitz 《Biochemical and biophysical research communications》2010,400(1):78-82
Bacterial ghosts (BGs) as non-living bacterial envelopes devoid of cytoplasmic content with preserved and intact inner and outer membrane structures of their living counterparts have been used to study the ability of their surface components for the induction of antimicrobial peptides and pro-inflammatory cytokines in human primary keratinocytes (KCs). Quantitative real-time PCR analysis revealed that incubation of KCs with BGs generated from wild-type Escherichia coli induced the mRNA expression of antimicrobial psoriasin (S100A7c) in a BGs particle concentration-dependent manner. Using immunoblot analysis we showed that BGs generated from the flagellin-deficient (ΔFliC) E. coli strain NK9375 were as effective as its isogenic wild-type (wt) E. coli strain NK9373 to induce psoriasin expression when normalized to BG particles being taken up by KCs. However, results obtained from endocytic activity of KCs reflect that internalization of BGs is greatly dependent on the presence of flagellin on the surface of BGs. Moreover, BGs derived from wt E. coli NK9373 strongly induced the release of the pro-inflammatory cytokines IL-6 and IL-8, compared to ΔFliC E. coli NK9375 BGs. Taken together, obtained data demonstrate that non-living BGs possessing all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat have the capacity to induce the expression of innate immune modulators and that these responses are partially dependent on the presence of flagellin. 相似文献
58.
Wittenburg H Lyons MA Li R Kurtz U Wang X Mössner J Churchill GA Carey MC Paigen B 《Journal of lipid research》2006,47(8):1780-1790
To identify additional loci that influence lipoprotein cholesterol levels, we performed quantitative trait locus (QTL) mapping in offspring of PERA/EiJxI/LnJ and PERA/EiJxDBA/2J intercrosses and in a combined data set from both crosses after 8 weeks of consumption of a high fat-diet. Most QTLs identified were concordant with homologous chromosomal regions that were associated with lipoprotein levels in human studies. We detected significant new loci for HDL cholesterol levels on chromosome (Chr) 5 (Hdlq34) and for non-HDL cholesterol levels on Chrs 15 (Nhdlq9) and 16 (Nhdlq10). In addition, the analysis of combined data sets identified a QTL for HDL cholesterol on Chr 17 that was shared between both crosses; lower HDL cholesterol levels were conferred by strain PERA. This QTL colocalized with a shared QTL for cholesterol gallstone formation detected in the same crosses. Haplotype analysis narrowed this QTL, and sequencing of the candidate genes Abcg5 and Abcg8 confirmed shared alleles in strains I/LnJ and DBA/2J that differed from the alleles in strain PERA/EiJ. In conclusion, our analysis furthers the knowledge of genetic determinants of lipoprotein cholesterol levels in inbred mice and substantiates the hypothesis that polymorphisms of Abcg5/Abcg8 contribute to individual variation in both plasma HDL cholesterol levels and susceptibility to cholesterol gallstone formation. 相似文献
59.
60.
Gerhard Fierlbeck Tilmann Schreiner Gernot Rassner 《Cancer immunology, immunotherapy : CII》1995,40(3):157-164
The effect of 13-cis-retinoic acid and highly purified human leukocyte interferon α (Alphaferon) therapy for metastatic melanoma was studied.
A group of 17 patients with disseminated malignant melanoma were treated over a 6-month period. They received 60 mg 13-cis-retinoic acid/day continuously and ten cycles of interferon α (IFNα). IFN was administered by subcutaneous injection, at
a daily dose of 6×106 IU Alphaferon. The 5-day treatment period was followed by an IFN-free interval of 2 weeks. We were able to observe an overall
response rate of 30% with 12% complete responses (2 out of 17 patients). Sites of response included the skin, lung, liver
and lymph nodes. All responses have now lasted over 6 months. Therapy was generally well tolerated and could be performed
on an outpatient basis. Side-effects of this combination therapy did not exceed the established side-effects of the two substances.
We also studied 2′-5′-oligoadenylate synthetase, β2-microglobulin and neopterin levels during the whole treatment course.
All patients were within the normal range before treatment and a sharp rise occurred during each IFN cycle. The maximum being
observed 24 h after the third injection. This indicates a high biological activity of IFNα administered cyclicly during the
whole treatment course. This finding also corresponds well with the absence of neutralizing antibodies before and after the
whole treatment period.
Received: 8 December 1994 / Accepted: 10 January 1995 相似文献