全文获取类型
收费全文 | 1968篇 |
免费 | 109篇 |
出版年
2021年 | 24篇 |
2020年 | 11篇 |
2019年 | 15篇 |
2018年 | 18篇 |
2017年 | 14篇 |
2016年 | 19篇 |
2015年 | 35篇 |
2014年 | 51篇 |
2013年 | 95篇 |
2012年 | 99篇 |
2011年 | 96篇 |
2010年 | 63篇 |
2009年 | 60篇 |
2008年 | 104篇 |
2007年 | 98篇 |
2006年 | 116篇 |
2005年 | 97篇 |
2004年 | 94篇 |
2003年 | 85篇 |
2002年 | 91篇 |
2001年 | 49篇 |
2000年 | 32篇 |
1999年 | 50篇 |
1998年 | 33篇 |
1997年 | 24篇 |
1996年 | 12篇 |
1995年 | 17篇 |
1994年 | 22篇 |
1993年 | 15篇 |
1992年 | 39篇 |
1991年 | 21篇 |
1990年 | 26篇 |
1989年 | 42篇 |
1988年 | 32篇 |
1987年 | 18篇 |
1986年 | 17篇 |
1985年 | 26篇 |
1984年 | 44篇 |
1983年 | 20篇 |
1982年 | 34篇 |
1981年 | 23篇 |
1980年 | 25篇 |
1979年 | 22篇 |
1978年 | 16篇 |
1977年 | 22篇 |
1976年 | 15篇 |
1975年 | 12篇 |
1973年 | 11篇 |
1971年 | 9篇 |
1968年 | 12篇 |
排序方式: 共有2077条查询结果,搜索用时 125 毫秒
991.
Structures and biological activities of peptidoglycans of Listeria monocytogenes and Propionibacterium acnes 总被引:5,自引:0,他引:5
K Kamisango I Saiki Y Tanio H Okumura Y Araki I Sekikawa I Azuma Y Yamamura 《Journal of biochemistry》1982,92(1):23-33
The cell-wall skeletons of Listeria monocytogenes strain EGD and Propionibacterium acnes strain C7, which have the ability to induce macrophage activation, were analyzed, and the structures of the peptidoglycans were investigated. The analytical data indicate that both peptidoglycans have glucosamine residues with free amino groups, which are responsible for the resistance to lysozyme. Possible structures of these peptidoglycans were deduced from the composition and the results of determination of N- and C-terminal amino acids, together with the characterization of fragments obtained by enzymatic treatment and partial acid hydrolysis of both peptidoglycans. The results suggested that the peptidoglycan of L. monocytogenes contains a cross-linkage region of peptide chains with meso-diaminopimelic acid and D-alanine, which belongs to the A1 gamma type (Schleifer, K.H. & Kandler, O. (1972) Bacteriol. Rev. 36, 407-477), whereas the peptidoglycan of P. acnes contains a cross-linkage region of peptide chains with L,L-diaminopimelic acid and D-alanine, in which two glycine residues combine with amino and carboxyl groups of two L,L-diaminopimelic acid residues. The latter type should be classified as a new type. These cell-wall skeletons and peptidoglycans were shown to have immunoadjuvant activity on the induction of delayed-type hypersensitivity and suppressive activity on the growth of 3-methylcholanthrene-induced fibrosarcoma in BALB/c mice, and the peptidoglycans were shown to be an immunological-active principle of these cell-wall skeletons. 相似文献
992.
Regional heterogeneity of benzodiazepine receptors at 37 degrees C: an in vitro study in various regions of the rat brain 总被引:1,自引:0,他引:1
The most compelling pharmacological evidence in support of benzo-diazepine (BZD) receptor heterogeneity is derived from the study of the complex interactions of CL 218872 and propyl beta-carboline-3-carboxylate (PCC) with brain BZD receptors. In the present study, we provide evidence to support the hypothesis that intraregional BZD receptor heterogeneity in rat brain is a result of the different conformational states of a single receptor. This hypothesis is based upon the observation that CL 218872 and PCC lose the ability to effectively discriminate BZD receptor subtypes in rat cerebral cortex, hippocampus and pons-medulla at physiological temperature (37 degrees C). Interestingly, both PCC and CL 218872 show higher affinity for BZD receptors in the cerebellum when compared to other brain regions at 37 degrees C. This observation suggests that interregional BZD receptor heterogeneity occurs under physiologically relevant temperatures. We propose that distinct cerebellar and non-cerebellar type BZD receptors exist in vivo while marked differences in the affinity of the type I and type II BZD receptor subtypes postulated by Klepner et al. 1979 may only occur in vitro at 0 degree--4 degree C. 相似文献
993.
Lipid rafts are functional microdomains enriched with sphingolipids and cholesterol. The fatty acyl chain composition of sphingolipids is a critical factor in the localization of lipids in lipid rafts. The recent studies suggest that lipid rafts are more heterogeneous than previously thought. In addition, our discovery of a new glycolipid, phosphatidylglucoside (PtdGlc), also supports the notion of raft heterogeneity. The complete structural characterization of PtdGlc shows that it consists solely of saturated fatty acyl chains: C18:0 at the sn-1 and C20:0 at the sn-2 positions of the glycerol backbone. This unique fatty acyl composition comprising a single molecular species rarely occurs in known mammalian lipids. Although the structure of PtdGlc is similar to that of phosphatidylinositol, PtdGlc localizes to the outer leaflet of the plasma membrane and is possibly involved in cell-cell interaction signaling in the central nervous system. 相似文献
994.
Kondo A Hirayama N Sugito Y Shono M Tanaka T Kitamura N 《The Journal of biological chemistry》2008,283(3):1428-1436
Activation of the extracellular signal-regulated kinase (ERK) pathway is a key factor in the regulation of cell proliferation by growth factors. Hepatocyte growth factor (HGF)-induced cell cycle arrest in the human hepatocellular carcinoma cell line HepG2 requires strong activation of the ERK pathway. In this study, we investigated the molecular mechanism of the activation. We constructed a chimeric receptor composed of the extracellular domain of the NGF receptor and the cytoplasmic domain of the HGF receptor (c-Met) and introduced a point mutation (N1358H) into the chimeric receptor, which specifically abrogates the direct binding of Grb2 to c-Met. The mutant chimeric receptor failed to mediate the strong activation of ERK, up-regulation of the expression of a Cdk inhibitor p16(INK4a) and inhibition of HepG2 cell proliferation by ligand stimulation. Moreover, the mutant receptor did not induce tyrosine phosphorylation of the docking protein Gab1. Knockdown of Gab1 using siRNA suppressed the HGF-induced strong activation of ERK and inhibition of HepG2 cell proliferation. These results suggest that coupling of Grb2 to Gab1 mediates the HGF-induced strong activation of the ERK pathway, which is required for the inhibition of HepG2 cell proliferation. 相似文献
995.
Fujiwara K Daido S Yamamoto A Kobayashi R Yokoyama T Aoki H Iwado E Shinojima N Kondo Y Kondo S 《The Journal of biological chemistry》2008,283(1):388-397
Programmed cell death (PCD) is involved in a variety of biologic events. Based on the morphologic appearance of the cells, there are two types of PCD as follows: apoptotic (type I) and autophagic (type II). However, the molecular machinery that determines the type of PCD is poorly defined. The purpose of this study was to show whether the presence of the cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1), a modulator of apoptosis, determines which type of PCD the cell undergoes. Treatment with C(2)-ceramide was associated with both the cleavage of caspase-3 and poly(ADP-ribose) polymerase and the degradation of autophagy-related Beclin 1 and Atg5 proteins, without a change in the cyclin-CDK activity, which culminated in apoptosis in p21(+/+) mouse embryonic fibroblasts (MEFs). On the other hand, C(2)-ceramide did not cleave caspase-3 or poly(ADP-ribose) polymerase and kept Beclin 1 and Atg5 proteins stable in p21(-/-) MEFs, events that this time culminated in autophagy. When expression of the p21 protein was inhibited by small interfering RNA or when the overexpression of Beclin 1 or Atg5 was induced, autophagy rather than apoptosis was initiated in the p21(+/+) MEFs treated with C(2)-ceramide. In contrast, the exogenous expression of p21 or the silencing of Beclin 1 and Atg5 with small interfering RNA increased the number of apoptotic cells and decreased the number of autophagic cells among C(2)-ceramide-treated p21(-/-) MEFs. gamma-Irradiation, which endogenously generates ceramide, induced a similar tendency in these MEFs. These results suggest that p21 plays an essential role in determining the type of cell death, positively for apoptosis and negatively for autophagy. 相似文献
996.
Blocking CD147 induces cell death in cancer cells through impairment of glycolytic energy metabolism
Baba M Inoue M Itoh K Nishizawa Y 《Biochemical and biophysical research communications》2008,374(1):111-116
CD147 is a multifunctional transmembrane protein and promotes cancer progression. We found that the anti-human CD147 mouse monoclonal antibody MEM-M6/1 strongly induces necrosis-like cell death in LoVo, HT-29, WiDr, and SW620 colon cancer cells and A2058 melanoma cells, but not in WI-38 and TIG-113 normal fibroblasts. Silencing or overexpression of CD147 in LoVo cells enhanced or decreased the MEM-M6/1 induced cell death, respectively. CD147 is known to form complex with proton-linked monocarboxylate transporters (MCTs), which is critical for lactate transport and intracellular pH (pHi) homeostasis. In LoVo cells, CD147 and MCT-1 co-localized on the cell surface, and MEM-M6/1 inhibited the association of these molecules. MEM-M6/1 inhibited lactate uptake, lactate release, and reduced pHi. Further, the induction of acidification was parallel to the decrease of the glycolytic flux and intracellular ATP levels. These effects were not found in the normal fibroblasts. As cancer cells depend on glycolysis for their energy production, CD147 inhibition might induce cell death specific to cancer cells. 相似文献
997.
Mizuno A In Y Fujita Y Abiko F Miyagawa H Kitamura K Tomoo K Ishida T 《FEBS letters》2008,582(23-24):3439-3444
Although the alpha-helical Y(X)4Lvarphi containing region of eIF4E-binding protein (4EBP) is the major binding region with eukaryotic initiation factor 4E (eIF4E), the roles of its N- and C-terminal regions in the binding are hardly known. To clarify the roles of these flexible regions in the interaction, the binding features of the sequentially N-, C-, or both-terminal-residue-deleted 4EBP2 mutants were investigated by surface plasmon resonance (SPR) analysis. It was shown that the C-terminal His74-Glu89 sequence has an auxiliary, but indispensable, function in stabilizing the binding to eIF4E. The possible interaction with eIF4E was estimated by molecular dynamics simulation. This is the first report on the importance of the C-terminal flexible region in the eIF4E-binding regulation of 4EBP. 相似文献
998.
Minoru Suzuki Yoshinori Takahashi Yasuko Mitome Taiji Itoh Tsuyoshi Abe Michio Masuda 《Phytochemistry》2002,60(8)
Two halogenated C15 acetogenins, itomanallenes A and B, with a terminal bromoallene moiety along with a halogenated sesquiterpene, itomanol, have been isolated from the red alga Laurencia intricata collected in Okinawan waters. Their structures were deduced from 1D and 2D NMR experiments including 1H–1H COSY, HSQC, HMBC, and NOESY methods. The alcohol corresponding to itomanallene B seems to be a plausible precursor of itomanallene A, which has an unusual 2,10-dioxabicyclo[7.3.0]dodecene skeleton. Itomanol was found to be a selinane-type bromosesquiterpenoid, and is the first example of a selinane to be isolated from Japanese Laurencia species. 相似文献
999.
Noriyuki Murai Akihiro Shimizu Yasuko Murakami Senya Matsufuji 《Journal of cellular biochemistry》2009,108(4):1012-1021
Antizymes (AZs) are polyamine‐induced proteins that negatively regulate cellular polyamine synthesis and uptake. Three antizyme isoforms are conserved among mammals. AZ1 and AZ2 have a broad tissue distribution, while AZ3 is testis specific. Both AZ1 and AZ2 inhibit ornithine decarboxylase (ODC) activity by binding to ODC monomer and target it to the 26S proteasome at least in vivo. Both also inhibit extra‐cellular polyamine uptake. Despite their being indistinguishable by these criteria, we show here using enhanced green fluorescent protein (EGFP)‐AZ2 fusion protein that in mammalian cells, the subcellular location of AZ2 is mainly in the nucleus, and is different from that of AZ1. The C‐terminal part of AZ2 is necessary for the nuclear distribution. Within a few hours, a shift in the distribution of EGFP‐AZ2 fusion protein from cytoplasm to the nucleus or from nucleus to cytoplasm is observable in NIH3T3 cells. In addition, we found that in cells a majority of AZ2, but not AZ1, is phosphorylated at Ser‐186, likely by protein kinase CK2. There may be a specific function of AZ2 in the nucleus. J. Cell. Biochem. 108: 1012–1021, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
1000.