全文获取类型
收费全文 | 2155篇 |
免费 | 119篇 |
国内免费 | 1篇 |
出版年
2022年 | 4篇 |
2021年 | 25篇 |
2020年 | 13篇 |
2019年 | 9篇 |
2018年 | 27篇 |
2017年 | 17篇 |
2016年 | 33篇 |
2015年 | 64篇 |
2014年 | 77篇 |
2013年 | 109篇 |
2012年 | 124篇 |
2011年 | 122篇 |
2010年 | 81篇 |
2009年 | 73篇 |
2008年 | 105篇 |
2007年 | 146篇 |
2006年 | 125篇 |
2005年 | 137篇 |
2004年 | 158篇 |
2003年 | 130篇 |
2002年 | 104篇 |
2001年 | 54篇 |
2000年 | 45篇 |
1999年 | 41篇 |
1998年 | 40篇 |
1997年 | 32篇 |
1996年 | 31篇 |
1995年 | 22篇 |
1994年 | 20篇 |
1993年 | 13篇 |
1992年 | 35篇 |
1991年 | 21篇 |
1990年 | 22篇 |
1989年 | 16篇 |
1988年 | 20篇 |
1987年 | 30篇 |
1986年 | 16篇 |
1985年 | 11篇 |
1984年 | 11篇 |
1983年 | 11篇 |
1982年 | 14篇 |
1981年 | 13篇 |
1980年 | 11篇 |
1979年 | 10篇 |
1978年 | 8篇 |
1977年 | 8篇 |
1975年 | 11篇 |
1974年 | 8篇 |
1973年 | 5篇 |
1972年 | 3篇 |
排序方式: 共有2275条查询结果,搜索用时 15 毫秒
991.
Minami Y Morishita Y Yamamoto T Iijima T Fukasawa M Ishikawa S Ichimura H Noguchi M 《Acta cytologica》2004,48(2):243-248
BACKGROUND: Pulmonary papillary adenoma is a benign pulmonary neoplasm. Previously pulmonary papillary adenoma was described in terms of immunohistochemistry and ultrastructure. However, there are no previous reports describing the cytologic characteristics of pulmonary papillary adenoma. CASE: A 50-year-old male was admitted for evaluation of a coin lesion in the left upper lung field. Radiologic images showed a solid, round tumor approximately 25 mm in diameter in the left upper lung. Transbronchial needle aspiration biopsy (TBNA) was performed, and small numbers of atypical cells were collected. Adenocarcinoma was suggested clinically, and left upper segmentectomy was performed. The histologic diagnosis was pulmonary papillary adenoma. Imprint cytology of the cut surface of the tumor showed tumor cells arranged in sheets that contained scant or vesicular cytoplasm. The nuclei were oval or round, without obvious anisokaryosis, and their chromatin was fine, without hyperchromasia. Cytologically, the nuclei of the tumor cells in the imprint specimen (38.70 +/- 8.69 microns 2) were uniform in size and similar to the atypical cells in the TBNA specimen (38.29 +/- 11.56 microns 2) but significantly larger than the nuclei of the bronchial cells (23.61 +/- 5.98 microns 2) (P < .0001). CONCLUSION: The cytologic appearance of pulmonary papillary adenoma was characterized morphologically and morphometrically. The possibility of cytodiagnosis by TBNA was suggested. 相似文献
992.
The export of bulk poly(A)(+) mRNA is blocked under heat-shocked (42 degrees C) conditions in Saccharomyces cerevisiae. We found that an mRNA export factor Gle2p rapidly dissociated from the nuclear envelope and diffused into the cytoplasm at 42 degrees C. However, in exponential phase cells pretreated with mild heat stress (37 degrees C for 1 h), Gle2p did not dissociate at 42 degrees C, and the export of bulk poly(A)(+) mRNA continued. Cells in stationary phase also continued with the export of bulk poly(A)(+) mRNA at 42 degrees C without the dissociation of Gle2p from the nuclear envelope. The dissociation of Gle2p was caused by increased membrane fluidity and correlated closely with blocking of the export of bulk poly(A)(+) mRNA. Furthermore, the mutants gle2Delta and rip1Delta could not induce such an adaptation of the export of bulk poly(A)(+) mRNA to heat shock. Our findings indicate that Gle2p plays a crucial role in mRNA export especially under heat-shocked conditions. Our findings also indicate that the nuclear pore complexes that Gle2p constitutes need to be stabilized for the adaptation and that the increased membrane integrity caused by treatment with mild heat stress or by survival in stationary phase is likely to contribute to the stabilization of the association between Gle2p and the nuclear pore complexes. 相似文献
993.
Murai-Takebe R Noguchi T Ogura T Mikami T Yanagi K Inagaki K Ohnishi H Matozaki T Kasuga M 《The Journal of biological chemistry》2004,279(12):11616-11625
Misfolding of proteins during endoplasmic reticulum (ER) stress results in the formation of cytotoxic aggregates. The ER-associated degradation pathway counteracts such aggregation through the elimination of misfolded proteins by the ubiquitin-proteasome system. We now show that SHP substrate-1 (SHPS-1), a transmembrane glycoprotein that regulates cytoskeletal reorganization and cell-cell communication, is a physiological substrate for the Skp1-Cullin1-NFB42-Rbx1 (SCF(NFB42)) E3 ubiquitin ligase, a proposed mediator of ER-associated degradation. SCF(NFB42) mediated the polyubiquitination of immature SHPS-1 and its degradation by the proteasome. Ectopic expression of NFB42 both suppressed the formation of aggresome-like structures and the phosphorylation of the translational regulator eIF2alpha induced by overproduction of SHPS-1 as well as increased the amount of mature SHPS-1 at the cell surface. An NFB42 mutant lacking the F box domain had no such effects. Our results suggest that SCF(NFB42) regulates SHPS-1 biosynthesis in response to ER stress. 相似文献
994.
Nonami A Kato R Taniguchi K Yoshiga D Taketomi T Fukuyama S Harada M Sasaki A Yoshimura A 《The Journal of biological chemistry》2004,279(50):52543-52551
Sprouty/Spred family proteins have been identified as negative regulators of growth factor-induced ERK/mitogen-activated protein (MAP) kinase activation. However, it has not been clarified whether these proteins regulate cytokine-induced ERK activity. We found that Spred-1 is highly expressed in interleukin-3 (IL-3)-dependent hematopoietic cell lines and bone marrow-derived mast cells. To investigate the roles of Spred-1 in hematopoiesis, we expressed wild-type Spred-1 and a dominant negative form of Spred-1, DeltaC-Spred, in IL-3- and stem cell factor (SCF)-dependent cell lines as well as hematopoietic progenitor cells from mouse bone marrow by retrovirus gene transfer. In IL-3-dependent Ba/F3 cells expressing c-kit, forced expression of Spred-1 resulted in a reduced proliferation rate and ERK activation in response to not only SCF but also IL-3. In contrast, DeltaC-Spred augmented IL-3-induced cell proliferation and ERK activation. Wild-type Spred-1 inhibited colony formation of bone marrow cells in the presence of cytokines, whereas DeltaC-Spred-1 expression enhanced colony formation. Augmentation of ERK activation and proliferation in response to IL-3 was also observed in Spred-1-deficient bone marrow-derived mast cells. These data suggest that Spred-1 negatively regulates hematopoiesis by suppressing not only SCF-induced but also IL-3-induced ERK activation. 相似文献
995.
The receptor tyrosine kinase Ror2 associates with and is activated by casein kinase Iepsilon 总被引:1,自引:0,他引:1
Kani S Oishi I Yamamoto H Yoda A Suzuki H Nomachi A Iozumi K Nishita M Kikuchi A Takumi T Minami Y 《The Journal of biological chemistry》2004,279(48):50102-50109
Ror2, a member of the mammalian Ror family of receptor tyrosine kinases, plays important roles in developmental morphogenesis, although the mechanism underlying activation of Ror2 remains largely elusive. We show that when expressed in mammalian cells, Ror2 associates with casein kinase Iepsilon (CKIepsilon), a crucial regulator of Wnt signaling. This association occurs primarily via the cytoplasmic C-terminal proline-rich domain of Ror2. We also show that Ror2 is phosphorylated by CKIepsilon on serine/threonine residues, in its C-terminal serine/threonine-rich 2 domain, resulting in autophosphorylation of Ror2 on tyrosine residues. Furthermore, it was found that association of Ror2 with CKIepsilon is required for its serine/threonine phosphorylation by CKIepsilon. Site-directed mutagenesis of tyrosine residues in Ror2 reveals that the sites of phosphorylation are contained among the five tyrosine residues in the proline-rich domain but not among the four tyrosine residues in the tyrosine kinase domain. Moreover, we show that in mammalian cells, CKIepsilon-mediated phosphorylation of Ror2 on serine/threonine and tyrosine residues is followed by the tyrosine phosphorylation of G protein-coupled receptor kinase 2, a kinase with a developmental expression pattern that is remarkably similar to that of Ror2. Intriguingly, a mutant of Ror2 lacking five tyrosine residues, including the autophosphorylation sites, fails to tyrosine phosphorylate G protein-coupled receptor kinase 2. This indicates that autophosphorylation of Ror2 is required for full activation of its tyrosine kinase activity. These findings demonstrate a novel role for CKIepsilon in the regulation of Ror2 tyrosine kinase. 相似文献
996.
A novel role for the immunophilin FKBP52 in copper transport 总被引:2,自引:0,他引:2
Sanokawa-Akakura R Dai H Akakura S Weinstein D Fajardo JE Lang SE Wadsworth S Siekierka J Birge RB 《The Journal of biological chemistry》2004,279(27):27845-27848
FK506-binding protein 52 (FKBP52) is an immunophilin that possesses peptidylprolyl cis/trans-isomerase (PPIase) activity and is a component of a subclass of steroid hormone receptor complexes. Several recent studies indicate that immunophilins can regulate neuronal survival and nerve regeneration although the molecular mechanisms are poorly understood. To investigate the function of FKBP52 in the nervous system, we employed a yeast two-hybrid strategy using the PPIase domain (domain I) as bait to screen a neonatal rat dorsal root ganglia cDNA expression library. We identified an interaction between FKBP52 domain I and Atox1, a copper-binding metallochaperone. Atox1 interacts with Menkes disease protein and Wilson disease protein (WD) and functions in copper efflux. The interaction between FKBP52 and Atox1 was observed in both glutathione S-transferase pull-down experiments and when proteins were ectopically expressed in human embryonic kidney (HEK) 293T cells and was sensitive to FK506. Interestingly, the FKBP52/Atox1 interaction was enhanced when HEK 293T cells were cultured in copper-supplemented medium and decreased in the presence of the copper chelator, bathocuproine disulfate, suggesting that the interaction is regulated in part by intracellular copper. Overexpression of FKBP52 increased rapid copper efflux in (64)Cu-loaded cells, as did the overexpression of WD transporter. Taken together, our present findings suggest that FKBP52 is a component of the copper efflux machinery, and in so, may also promote neuroprotection from copper toxicity. 相似文献
997.
998.
999.
One of a pair of cerci was ablated in the first-, fourth- and last-instar nymphs of the cricket, Gryllus bimaculatus. The insects were then reared until the final molt, after which the intensity-response (I-R) relationships for four giant interneurons (GIs) 8-1, 9-1, 9-2 and 9-3 with regard to a controlled air current stimulus were measured. In order to examine the functional changes during postembryonic development and the differences in the physiological plasticity of GIs between nymphs and adults, the obtained I-R curves for each GI were compared with those measured in intact and unilaterally cercus-ablated adult crickets. Each GI showed a distinctive change in response magnitudes after the long-term unilateral cercal ablation. In most cases, the I-R curves for each GI in the crickets ablated from nymphal periods were different from those in the adult crickets mentioned above. Moreover, the pattern of change in response magnitude was different from GI to GI. In contrast to these observations, it was reported that some important characteristics of the wind-evoked escape behavior such as relative occurrence and escape direction in unilaterally cercus-ablated crickets investigated after a long-term rearing were almost identical with those in intact crickets. Therefore, the results obtained in the present study suggest that functional changes occur not only in GIs but also in many other neural elements in the escape-eliciting system in order to maintain the features of wind-evoked escape behavior. 相似文献
1000.
Kusui K Sasaki H Adachi R Matsui S Yamamoto K Yamaguchi T Kasahara T Suzuki K 《Molecular and cellular biochemistry》2004,262(1-2):187-193
We previously reported that an actin-binding protein, cofilin, is involved in superoxide production, phagocytosis, and chemotaxis in activated phagocytes through cytoskeletal reorganization. To elucidate the functions of cofilin in greater detail we tried to identify cofilin-binding proteins by using a phage-displayed cDNA library constructed from human brain mRNAs. Several phage clones capable of binding to cofilin were obtained, and the phage with the strongest binding affinity contained the C-terminal half of ribosomal protein S18. To confirm the interaction between the S18 protein and cofilin, we investigated whether cofilin would bind to His-tagged S18 protein immobilized in Ni-NTA-agarose gel. Cofilin and the S18 protein co-eluted with a low pH (4.5) buffer, suggesting that the proteins interact with each other. Preincubation of cofilin with actin abrogated the binding to protein S18, indicating that cofilin interacts with S18 protein at the actin-binding site, and cofilin co-immunoprecipitated with FLAG-tagged S18 protein expressed in COS-7 cells. These results suggest that some cofilin molecules bind the ribosomal S18 protein under physiological conditions. 相似文献