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991.
992.
Yamauchi J Hirasawa A Miyamoto Y Kokubu H Nishii H Okamoto M Sugawara Y Tsujimoto G Itoh H 《Biochemical and biophysical research communications》2002,296(1):85-92
We previously reported that the alpha1B-adrenergic receptor leads to activation of Rho family small GTPases, and in turn, c-Jun N-terminal kinase (JNK), which results in the inhibition of cell proliferation. Here, we show the involvement of the Rho family guanine nucleotide exchange factor (GEF) Dbl's Big Sister (Dbs) in the signaling pathway. Transfection of a Dbl-homology (DH) and pleckstrin-homology (PH) domain-deficient form of Dbs into cells blocked the alpha1B-adrenergic receptor-induced activation of JNK. Conversely, transfection of an isolated DH domain of Dbs induced JNK activation. Stimulation of the alpha1B-adrenergic receptor enhanced an intrinsic Cdc42-GEF activity of Dbs in a manner dependent on Src family tyrosine kinases. Additionally, DH and PH domain deficient Dbs blocked the receptor-induced inhibition of cell proliferation, while DH domain of Dbs inhibited cell proliferation via the JNK-dependent pathway. Taken together, Dbs may play an important role in the anti-mitogenic JNK pathway downstream of the alpha1B-adrenergic receptor. 相似文献
993.
Nakagawa Y Okada S Hatano M Ebara M Saisho H Tokuhisa T 《Journal of biochemistry and molecular biology》2002,35(5):452-458
Exposure to ultraviolet light (UV) induces apoptosis in mammalian cells. The caspase group of proteases is required for the apoptosis. This pathway is initiated by a release of cytochrome c from the mitochondria into the cytosol. Several Bcl-2 family proteins can regulate the release of cytochrome c by stabilizing the mitochondrial membrane. Here we show that expression of the endogenous bcl-xL was strongly downregulated in NIH3T3 cells within 2 h after UV-C irradiation, and that of bax was upregulated from 8 h after irradiation. Apoptosis was induced in more than 50% of the NIH3T3 cells 48 h after irradiation. Constitutive overexpression of bcl-xL in NIH3T3 cells protected the UV-induced apoptosis by preventing the loss of mitochondrial membrane potential and the activation of caspase 9. These results suggest that downregulation of Bcl-xL is relevant to UV-induced apoptosis of fibroblasts. 相似文献
994.
995.
Shibukaw A Yoshikawa Y Kimura T Kuroda Y Nakagawa T Wainer IW 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2002,768(1):189-197
Plasma protein binding of N-desethyloxybytynin (DEOXY), a major active metabolite of oxybutynin (OXY), was investigated quantitatively and enantioselectively using high-performance frontal analysis (HPFA). An on-line HPLC system which consists of HPFA column, extraction column and analytical column was developed to determine the unbound concentrations of DEOXY enantiomers in human plasma, in human serum albumin (HSA) solutions, and in human alpha1-acid glycoprotein (AGP) solutions. DEOXY is bound in human plasma strongly and enantioselectively. The unbound drug fraction in human plasma samples containing 5 microM (R)- or (S)-DEOXY was 1.19 +/- 0.001 and 2.33 +/- 0.044%, respectively. AGP plays the dominant role in this strong and enantioselective plasma protein binding of DEOXY. The total binding affinity (nK) of (R)-DEOXY and (S)-DEOXY to AGP was 2.97 x 10(7) and 1.31 x 10(7) M(-1), respectively, while the nK values of (R)-DEOXY and (S)-DEOXY to HSA were 7.77 x 10(3) and 8.44 x 10(3) M(-1), respectively. While the nK value of (S)-DEOXY is weaker than that of (S)-OXY (1.53 x 10(7) M(-1)), the nK value of (R)-DEOXY is 4.33 times stronger than that of (R)-OXY (6.86 x I0(6) M(-1)). This suggests that the elimination of an ethyl group weakens the binding affinity of the (S)-isomer because of the decrease in hydrophobicity, while the binding affinity of the (R)-isomer is enhanced by the decrease in steric hindrance. The total binding affinity of DEOXY to HSA is much lower than that of DEOXY-AGP binding as well as OXY-HSA binding (2.64 x 10(4) and 2.19 x 10(4) M(-1) for (R)-OXY and (S)-OXY, respectively). The study on competitive binding between OXY and DEOXY indicated that DEOXY enantiomers and OXY enantiomers are all bound competitively at the same binding site of AGP molecule. 相似文献
996.
Requirement for Activation of the Serine-Threonine Kinase Akt (Protein Kinase B) in Insulin Stimulation of Protein Synthesis but Not of Glucose Transport 总被引:17,自引:6,他引:11
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Tadahiro Kitamura Wataru Ogawa Hiroshi Sakaue Yasuhisa Hino Shoji Kuroda Masafumi Takata Michihiro Matsumoto Tetsuo Maeda Hiroaki Konishi Ushio Kikkawa Masato Kasuga 《Molecular and cellular biology》1998,18(7):3708-3717
A wide variety of biological activities including the major metabolic actions of insulin is regulated by phosphatidylinositol (PI) 3-kinase. However, the downstream effectors of the various signaling pathways that emanate from PI 3-kinase remain unclear. Akt (protein kinase B), a serine-threonine kinase with a pleckstrin homology domain, is thought to be one such downstream effector. A mutant Akt (Akt-AA) in which the phosphorylation sites (Thr308 and Ser473) targeted by growth factors are replaced by alanine has now been shown to lack protein kinase activity and, when overexpressed in CHO cells or 3T3-L1 adipocytes with the use of an adenovirus vector, to inhibit insulin-induced activation of endogenous Akt. Akt-AA thus acts in a dominant negative manner in intact cells. Insulin-stimulated protein synthesis, which is sensitive to wortmannin, a pharmacological inhibitor of PI 3-kinase, was abolished by overexpression of Akt-AA without an effect on amino acid transport into the cells, suggesting that Akt is required for insulin-stimulated protein synthesis. Insulin activation of p70 S6 kinase was inhibited by ~75% in CHO cells and ~30% in 3T3-L1 adipocytes, whereas insulin-induced activation of endogenous Akt was inhibited by 80 to 95%, by expression of Akt-AA. Thus, Akt activity appears to be required, at least in part, for insulin stimulation of p70 S6 kinase. However, insulin-stimulated glucose uptake in both CHO cells and 3T3-L1 adipocytes was not affected by overexpression of Akt-AA, suggesting that Akt is not required for this effect of insulin. These data indicate that Akt acts as a downstream effector in some, but not all, of the signaling pathways downstream of PI 3-kinase. 相似文献
997.
Atsuo Taniguchi Masayuki Hakoda Hisashi Yamanaka Chihiro Terai Keiji Hikiji Ryuji Kawaguchi Noriko Konishi Sadao Kashiwazaki N. Kamatani 《Human genetics》1998,102(2):197-202
Adenine phosphoribosyltransferase (APRT) is a purine metabolic enzyme and a homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine
urolithiasis. Various germline abnormalities have been described, but we report here a unique type of germline mutation in
a homozygous individual (SY) who had excreted 2,8-dihydroxyadenine crystals. In SY, TCA was substituted for the physiological
stop codon TGA. This base substitution generates a new HinfI restriction site, and, using the polymerase chain reaction and subsequent digestion by this enzyme, it was confirmed that
SY is homozygous for the base substitution. This base change is unique in that it generates an open reading frame that extends
to the poly(A) addition site. The amount of mRNA in transformed B cells from SY was approximately a quarter of that in control
subjects and no APRT proteins were detected. In eukaryotes, unlike in prokaryotes, no rescue systems for defective polypeptide
termination caused by a missing stop codon have been found. Therefore, the outcome of the defect of SY is unclear from present
knowledge about termination of polypeptide synthesis. Investigations into the mechanisms of the absence of protein in the
cells of SY may lead to a better understanding of the physiological and nonphysiological termination of polypeptide synthesis
in eukaryotic cells.
Received: 26 August 1997 / Accepted: 5 November 1997 相似文献
998.
The chl a specific absorption coefficients [a* (λ), m2·mg chl a ? 1] were examined in chemostat culture of the Prymnesiophyceae Isochrysis galbana (Parke) under a 12:12‐h light:dark cycle at low light (75 μmol photons·m ? 2·s ? 1) and high light (500 μmol photons· m ? 2·s ? 1) conditions. Other associated measurements such as pigment composition, cell density, and diameter as the measure of cell size were also made at the two light regimes every 2 h for 2 days to confirm the periodicity. A distinct diel variability was observed for the a* (λ) with maxima near dawn and minima near dusk. The magnitude of diel variation in a* (440) was 15% at low light and 22% at high light. Pronounced diel patterns were observed for cell size with minima near dawn and maxima near dusk. The magnitude of diel variation in cell size was 9.3% at low light and 21% at high light. The absorption efficiency factors [Q a (440)] were determined by reconstruction using intracellular concentrations of pigments and cell size. The Q a (440) also showed a distinct diel variability, with minima near dawn and maxima near dusk. The diel variation in a* (λ) and Q a (λ) was primarily caused by changes in cell size due to growth, although there was some influence from diel variations in the intracellular pigment concentrations. The results presented here indicated that diel variation in a* (λ) was an important component of the optical characterization of phytoplankton. 相似文献
999.
1000.
This paper describes a monoclonal antibody that recognizes a molecule whose expression is mostly restricted to some of the forebrain areas that control singing behavior in adult estrildine species studied, including the zebra, Bengalese, and spice finches. When the song system displays extreme sexual dimorphism, as in these species, antibody staining occurs only in the male's song nuclei. However, protein expression is identical in both sexes of estrildine finches, in which females also have a well-developed song system. Canaries appear to lack the protein, but it can be induced in female zebra finches by early estrogen treatment. Antibody staining patterns in the zebra finch show that the protein's expression is developmentally regulated to coincide with the abrupt increase in the volume and cell size of the male's or the estrogen-treated female's song system. 相似文献