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931.
Grace W. C. Cheung Andrea Kokorovic Tony K. T. Lam 《Cellular and molecular life sciences : CMLS》2009,66(18):3023-3027
Upon the entry of nutrients into the small intestine, nutrient sensing mechanisms are activated to allow the body to adapt
appropriately to the incoming nutrients. To date, mounting evidence points to the existence of an upper intestinal lipid-induced
gut–brain neuronal axis to regulate energy homeostasis. Moreover, a recent discovery has also revealed an upper intestinal
lipid-induced gut–brain–liver neuronal axis involved in the regulation of glucose homeostasis. In this mini-review, we will
focus on the mechanisms underlying the activation of these respective neuronal axes by upper intestinal lipids. 相似文献
932.
G S Jimenez F Bryntesson M I Torres-Arzayus A Priestley M Beeche S Saito K Sakaguchi E Appella P A Jeggo G E Taccioli G M Wahl M Hubank 《Nature》1999,400(6739):81-83
Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage. 相似文献
933.
934.
Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome. 总被引:7,自引:0,他引:7
Thiamine-responsive megaloblastic anaemia syndrome (TRMA; MIM 249270) is an autosomal recessive disorder with features that include megaloblastic anaemia, mild thrombocytopenia and leucopenia, sensorineural deafness and diabetes mellitus. Treatment with pharmacologic doses of thiamine ameliorates the megaloblastic anaemia and diabetes mellitus. A defect in the plasma membrane transport of thiamine has been demonstrated in erythrocytes and cultured skin fibroblasts from TRMA patients. The gene causing TRMA was assigned to 1q23.2-q23.3 by linkage analysis. Here we report the cloning of a new gene, SLC19A2, identified from high-through-put genomic sequences due to homology with SLC19A1, encoding reduced folate carrier 1 (refs 8-10). We cloned the entire coding region by screening a human fetal brain cDNA library. SLC19A2 encodes a protein (of 497 aa) predicted to have 12 transmembrane domains. We identified 2 frameshift mutations in exon 2. a 1-bp insertion and a 2-bp deletion, among four Iranian families with TRMA. The sequence homology and predicted structure of SLC19A2, as well as its role in TRMA, suggest that its gene product is a thiamine carrier, the first to be identified in complex eukaryotes. 相似文献
935.
936.
E A Rogaeva S Premkumar J Grubber L Serneels W K Scott T Kawarai Y Song D L Hill S M Abou-Donia E R Martin J J Vance G Yu A Orlacchio Y Pei M Nishimura A Supala B Roberge A M Saunders A D Roses D Schmechel A Crane-Gatherum S Sorbi A Bruni G W Small P M Conneally J L Haines F Van Leuven P H St George-Hyslop L A Farrer M A Pericak-Vance 《Nature genetics》1999,22(1):19-22
937.
Temporal trends of perfluoroalkyl substances (PFASs) have been determined in the blood samples from several countries globally including a female population in Sweden recently, yet little is known about the time trends in the blood levels of these compounds in Swedish male populations over recent years. In this study, the fourteen target PFASs consisted of four perfluorosulfonates (PFSAs) and ten perfluorocarboxylates (PFCAs) in the whole blood samples, collected from 153 Swedish elderly men during the period between 2008 and 2010, were analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). As the dominant PFASs contaminants in the blood samples, perfluorooctane sulfo- nate (PFOS) showed the highest geometric mean (GM) at 8.5 ng/mL, ranging from 1.7 to 29 ng/mL, while blood perfluorooctanoic acid (PFOA) contained the GM of 1.8 ng/mL, ranging from 0.35 to 6.4 ng/mL. Both the levels of these two compounds were lower than those determined in the blood samples of Swedish elderly pop- ulations derived from the late 1990s. According to the temporal trend analysis, over the three years, the blood levels of PFOS in Swedish male populations declined 16 % per annum, while those of perfluoroundecanoic acid (PFUnDA) increased 6.1% per annum, which were con- sistent with those reported previously for the populations from other countries. 相似文献
938.
Thirty - nine Utah streams were sampled for cutthroat trout. Of these, 31 contain cutthroat or cutthroat / rainbow hybrid populations. By using starch gel electrophoresis, these populations were segregated into three groups. One group consisted predominately of fish from the Sevier River (of the Bonneville Basin) and Colorado drainages. A second was primarily populations from the Bear River Drainage (Bonneville Basin) as well as some scattered populations along the Wasatch Front (Bonneville Basin). The third consisted of Wasatch Front populations and populations that have hybridized with rainbow trout. Since different subspecies of cutthroat trout are native to the Colorado and Bonneville drainages, one would expect the populations from within the Bonneville Basin to be more similar to one another and less similar to the Colorado River populations. That this did not occur raises questions concerning the evolutionary relationships of the subspecies and the populations. It is clear that at least a northern (Bear River) and southern (Sevier River) form of the Bonneville cutthroat exists. The Wasatch Front may represent an intermediate zone where these two forms intergrade. 相似文献
939.
940.
Death of mature T cells by separate ligation of CD4 and the T-cell receptor for antigen 总被引:48,自引:0,他引:48
Effector T cells are restricted to recognizing antigens associated with major histocompatibility complex (MHC) molecules. Specific recognition is mediated by the alpha beta heterodimer of the T-cell receptor (TCR)/CD3 complex, although other membrane components are involved in T-cell antigen recognition and functions. There has been much controversy in this regard over the part played by the CD4 glycoprotein. It is known that expression of CD4 correlates closely with the cell's ability to recognize antigens bound to class II MHC molecules and that CD4 can bind to class II molecules. Also monoclonal antibodies to CD4 can modify signals generated through the TCR/CD3 complex. It has therefore been proposed that CD4 binds to class II molecules, coaggregates with the TCR-CD3 complex and aids the activation of T cells. But given that TCR can itself impart restriction on the cell, it remains unclear whether the contribution of CD4-derived signals to those generated through the TCR alpha beta-CD3 complex is central to this activation. Here we report that when preceded by ligation of CD4, signalling through TCR alpha beta results in T cell unresponsiveness due to the induction of activation dependent cell death by apoptosis. These results imply that CD4 is critically involved in determining the outcome of signals generated through TCR, and could explain why the induction of effector T cells needs to be MHC-restricted. 相似文献