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941.
Comparison of rat mesenchymal stem cells derived from bone marrow,synovium, periosteum,adipose tissue,and muscle 总被引:18,自引:0,他引:18
Yoshimura H Muneta T Nimura A Yokoyama A Koga H Sekiya I 《Cell and tissue research》2007,327(3):449-462
Mesenchymal stem cells (MSCs) are increasingly being reported as occurring in a variety of tissues. Although MSCs from human
bone marrow are relatively easy to harvest, the isolation of rodent MSCs is more difficult, thereby limiting the number of
experiments in vivo. To determine a suitable cell source, we isolated rat MSCs from bone marrow, synovium, periosteum, adipose,
and muscle and compared their properties for yield, expansion, and multipotentiality. After two passages, the cells in each
population were CD11b (−), CD45 (−), and CD90 (+). The colony number per nucleated cells derived from synovium was 100-fold
higher than that for cells derived from bone marrow. With regard to expansion potential, synovium-derived cells were the highest
in colony-forming efficiency, fold increase, and growth kinetics. An in vitro chondrogenesis assay demonstrated that the pellets
derived from synovium were heavier, because of their greater production of cartilage matrix, than those from other tissues,
indicating their superiority in chondrogenesis. Synovium-derived cells retained their chondrogenic potential after a few passages.
The Oil Red-O positive colony-rate assay demonstrated higher adipogenic potential in synovium- and adipose-derived cells.
Alkaline phosphatase activity was greater in periosteum- and muscle-derived cells during calcification. The yield and proliferation
potential of rat MSCs from solid tissues was much better than those from bone marrow. In particular, synovium-derived cells
had the greatest potential for both proliferation and chondrogenesis, indicating their usefulness for cartilage study in a
rat model.
This study was supported in part by grants from the Japan Latest Osteoarthritis Society and from the Center of Excellence
Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone in Tokyo Medical and Dental University
(to T.M.), and by the Japan Society for the Promotion of Science (grant no. 18591657 to I.S.). Recombinant human bone morphogenetic
protein-2 was kindly provided by Astellas Pharma. 相似文献
942.
Vogel CF Nishimura N Sciullo E Wong P Li W Matsumura F 《Archives of biochemistry and biophysics》2007,461(2):169-175
Activation of the aryl hydrocarbon receptor (AhR) by TCDD may lead to the induction of proinflammatory cytokines in various cell types and organs such as liver leading to active chronic inflammation. Here we studied the expression of the chemokines keratinocyte chemoattractant (KC) and monocyte chemoattractant protein 1 (MCP-1) in different organs of mice after exposure to TCDD. TCDD exposure led to an early and clear induction of KC in liver and spleen on day 1 which was sustained over a period of 10 days. The level of MCP-1 mRNA was induced by TCDD on day 1 in spleen, lung, kidney, and liver, which was further increased at day 7. Increase of KC and MCP-1 at day 7 in liver, thymus, kidney, adipose, and heart was associated with elevated levels of the macrophage marker F4/80, indicating the infiltration of macrophages in these organs. Induction of KC requires a functional AhR since mice with a mutation in the AhR nuclear localization domain (AhR(nls)) were found to be resistant to TCDD-induced expression of KC. These results are the first showing the induction of the chemokines KC and MCP-1 in multiple organs of mice associated with an increase of the macrophage marker F4/80 indicating the involvement in TCDD's inflammatory response like infiltration of macrophages. 相似文献
943.
944.
945.
GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease 总被引:5,自引:0,他引:5
Leucine-rich repeat kinase 2 (LRRK2), a product of a causative gene for the autosomal-dominant form of familial Parkinson's disease (PARK8), harbors a Ras-like small GTP binding protein-like (ROC) domain besides the kinase domain, although the relationship between these two functional domains remains elusive. Here we show by thin-layer chromatographic analysis that LRRK2 stably binds GTP but lacks a GTPase activity in HEK293 and Neuro-2a cells. A ROC domain mutation that converts LRRK2 to a guanine nucleotide-free form (T1348N) abolishes the kinase activity of LRRK2 as well as its phosphate incorporation upon metabolic labeling. The phosphorylation of LRRK2 was inhibited by potential inhibitors for cyclic AMP-dependent protein kinase. These data suggest that binding of GTP to the ROC domain regulates the kinase activity of LRRK2 as well as its phosphorylation by other kinase(s). 相似文献
946.
We cloned, expressed and characterized a novel alpha/beta-galactoside alpha2,3-sialyltransferase from Vibrio sp. bacterium JT-FAJ-16. Using a alpha2,3-sialyltransferase gene from a marine bacterium as a probe, a DNA sequence encoding a 402-amino-acid protein was identified from the JT-FAJ-16 genomic library. The protein showed 27.3-64.7% identity to the bacterial sialyltransferases classified into glycosyltransferase family 80. The protein showed sialyltransferase activity when expressed in Escherichia coli. The N-terminal truncated form of the enzyme was amplified in E. coli and its recovered activity was 215.7 unit/l culture medium. It was purified as a single band on SDS-PAGE through the three chromatographic steps. The specific activity of the purified recombinant enzyme reached 57.5 unit/mg protein. The alpha2,3sialylation was confirmed by (1)H- and (13)C-NMR analyses of the reaction products. The enzyme was optimally active at pH 5.5 and at 20 degrees C. Interestingly, the enzyme used both the alpha- and beta-anomers of galactosides as acceptors, suggesting that it can be described as an alpha/beta-galactoside alpha2,3-sialyltransferase. The enzyme had a wide range of acceptor substrate specificities. It transferred N-acetylneuraminic acid (NeuAc) to various monosaccharides and various oligosaccharides, and both N-linked and O-linked asialo-glycoprotein. These results suggest that the enzyme can be used as a powerful tool for the study for glycotechnology. 相似文献
947.
948.
Male mice lacking ADAM2 (fertilin beta) or ADAM3 (cyritestin) are infertile; cauda epididymal sperm (mature sperm) from these mutant mice cannot bind to the egg zona pellucida. ADAM3 is barely present in Adam2-null sperm, despite normal levels of this protein in Adam2-null testicular germ cells (TGCs; sperm precursor cells). Here, we have explored the molecular basis for the loss of ADAM3 in Adam2-null TGCs to clarify the biosynthetic and functional linkage of ADAM2 and ADAM3. A small portion of total ADAM3 was found present on the surface of wild-type and Adam2(-/-) TGCs at similar levels. In the Adam2-null TGCs, however, surface-localized ADAM3 exhibited an increased amount of an endoglycosidase H-resistant form that may be related to instability of ADAM3. Moreover, we found a complex between ADAM2 and ADAM3 on the surface of TGCs and sperm. The intracellular chaperone calnexin was a component of the testicular ADAM2-ADAM3 complex. Our findings suggest that the association with ADAM2 is a key element for stability of ADAM3 in epididymal sperm. The presence of the ADAM2-ADAM3 complex in sperm also suggests a potential role of ADAM2 with ADAM3 in sperm binding to the egg zona pellucida. 相似文献
949.
A recurrent mutation in type II collagen gene causes Legg-Calvé-Perthes disease in a Japanese family
Miyamoto Y Matsuda T Kitoh H Haga N Ohashi H Nishimura G Ikegawa S 《Human genetics》2007,121(5):625-629
Legg-Calvé-Perthes disease (LCPD) is a common childhood hip disorder characterized by sequential stages of involvement of
the capital femoral epiphyses, including subchondral fracture, fragmentation, re-ossification and healing with residual deformity.
Most cases are sporadic, but familial cases have been described, with some families having multiple affected members. Genetic
factors have been implicated in the etiology of LCPD, but the causal gene has not been identified. We have located a missense
mutation (p.G1170S) in the type II collagen gene (COL2A1) in a Japanese family with an autosomal dominant hip disorder manifesting as LCPD and showing considerable intra-familial
phenotypic variation. This is the first report of a mutation in hereditary LCPD. COL2A1 mutations may be more common in LCPD patients than currently thought, particularly in familial and/or bilateral cases. 相似文献
950.
Kano Y Soda K Nakamura T Saitoh M Kawakami M Konishi F 《Cancer immunology, immunotherapy : CII》2007,56(6):771-781
Increased blood polyamine levels, often observed in cancer patients, have negative impacts on patient prognosis and are associated
with tumor progression. The purpose of our study was to examine the effects of polyamines on cellular immune function. Peripheral
blood mononuclear cells (PBMCs) from healthy volunteers were cultured with the human natural polyamines spermine, spermidine,
or putrescine, and the effects on immune cell function were examined. The correlation between post-operative changes in blood
polyamine levels and lymphokine-activated killer (LAK) activity was also examined in cancer patients. Spermine decreased the
adhesion of non-stimulated PBMCs to tissue culture plastic in a dose- and a time-dependent manner without affecting cell viability
or activity. This decrease in adhesion capacity was accompanied by a decrease in the number of CD11a bright-positive and CD56
bright-positive cells. Upon stimulation with interleukin 2 to activate LAK cytotoxicity, PBMCs cultured overnight with 100
or 500 μM spermine showed decreased cytotoxic activity against Daudi cells (91.5 ± 1.7 and 84.9 ± 3.0%, respectively (n = 6) compared to PBMC cultured without polyamines). In a group of 25 cancer patients, changes in blood spermine levels after
surgery were negatively correlated with changes in LAK cytotoxicity after surgery (r = −0.510, P = 0.008: n = 25). Increased blood spermine levels may be an important factor in the suppression of anti-tumor immune cell function. 相似文献