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71.
Mutational screening of APP gene in patients with early-onset Alzheimer disease utilizing mismatched PCR-RFLP 总被引:1,自引:0,他引:1
Yumiko Nishiwaki Kouzin Kamino Aoi Yoshiiwa Keiko Nagano Masatoshi Takeda Hirotaka Tanabe Tsuyoshi Nishimura Toshiko Kobayashi Hideki Yamamoto Yasuhiro Nonomura Hiroshi Yoneda Toshiaki Sakai Masaki Imagawa Tetsuro Miki Toshio Ogihara 《Clinical genetics》1996,49(3):119-123
To elucidate the frequency of mutations of the β/A4 amyloid protein precursor (APP) gene in early-onset Alzheimer disease, we designed a mismatched PCR-RFLP that can identify all kinds of missense mutations at codon 717 in addition to the seven kinds of known mutations at exon 17. When we screened mutations at exon 17 utilizing this method and the double missense mutations at exon 16 of the APP gene by PCR-RFLP, no cases revealed mutations of the APP gene among 13 familial and 54 sporadic cases, except one family (OS-1) that had previously been reported and used as a positive control of APP717(Val → Ile). Our results support the hypothesis that mutations in the APP gene are not major causes in early-onset Alzheimer disease. 相似文献
72.
73.
Hanibuchi M Yano S Nishioka Y Yanagawa H Miki T Sone S 《Clinical & experimental metastasis》2000,18(5):353-360
The formation of metastases in multiple organs and acquired multi-drug resistance (MDR) are the major obstacles for treatment
of human small-cell lung cancer (SCLC). To explore the possibility of immunological overcoming of multiple-organ metastases
produced by refractory SCLC, we established the MDR variant (SBC-3/DOX), expressing P-glycoprotein, of parental SBC-3 cells
by culturing with gradually increasing concentration of adriamycin. Both SBC-3 and SBC-3/DOX cells expressed a high amount
of ganglioside GM2, an ideal target of SCLC cells. A mouse-human chimeric anti-GM2 monoclonal antibody (KM966) induced antibody-dependent
cellular cytotoxicity (ADCC) mediated by human mononuclear cells (lymphocytes and monocytes) and complement-dependent cytotoxicity
(CDC) mediated by human AB serum against SBC-3/DOX cells to a similar extent compared with parental SBC-3 cells. Pretreatment
of human effector cells with various cytokines induced further enhancement of the KM966-dependent ADCC against SBC-3/DOX cells.
Intravenous injection of SBC-3 or SBC-3/DOX cells into natural killer (NK) cell-depleted severe combined immunodeficient (SCID)
mice developed metastases in multiple organs (liver, kidneys and lymph nodes). Interestingly, SBC-3/DOX cells produced metastases
more rapidly than SBC-3 cells, suggesting more aggressive phenotype of SBC-3/DOX cells than their parental cells in vivo. Systemic treatment with KM966, given on days 2 and 7, drastically inhibited the formation of multiple-organ metastases produced
by both SBC-3 and SBC-3/DOX cells, indicating that KM966 can eradicate metastasis by SCLC cells irrespective of MDR phenotype.
These findings suggest that the mouse-human chimeric KM966 targets the GM2 antigen, and might be useful for the immunological
circumvention of multiple-organ metastases of refractory SCLC.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
74.
Kazunori Akiyoshi Toshio Masuda Toshinobu Higashimura 《Macromolecular chemistry and physics.》1992,193(3):755-763
Block copolymerizations of 1-chloro-1-octyne (1-ClO) with several substituted acetylenes were examined by means of living polymerization. o-(Trifluoromethyl)phenylacetylene (o-CF3PA), o-(trimethylsilyl)phenylacetylene (o-Me3SiPA), 1-chloro-2-phenylacetylene (1-ClPA), p-butyl-o,o,m,m-tetrafluorophenylacetylene (p-BuF4PA), and tert-butylacetylene (t-BuA) were used as comonomers, and the MoOCl4-n-Bu4Sn-EtOH (mole ratio 1:1:1) catalyst, which is known to effect living polymerization of substituted acetylenes, was employed. When o-CF3PA and 1-CIPA were the comonomers in combination with 1-CIO, block copolymers were exclusively obtained in both orders of monomer addition. In the cases of o-Me3SiPA and p-BuF4PA as comonomers, the copolymerizations initiated from 1-CIO produced block copolymers selectively, whereas the homopolymers of o-Me3SiPA and p-BuF4PA also formed if the order of monomer addition was reversed. The pair of 1-CIO and t-BuA did not selectively yield block copolymers irrespective of the order of monomer addition. Thus, block copolymerization occurred between 1-CIO and monomers that show high “livingness” and close reactivities. 相似文献
75.
ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis 总被引:9,自引:0,他引:9
Miki T Liss B Minami K Shiuchi T Saraya A Kashima Y Horiuchi M Ashcroft F Minokoshi Y Roeper J Seino S 《Nature neuroscience》2001,4(5):507-512
Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice. Although pancreatic alpha-cells were functional in Kir6.2-/-, the mice exhibited a severe defect in glucagon secretion in response to systemic hypoglycemia. In addition, they showed a complete loss of glucagon secretion, together with reduced food intake in response to neuroglycopenia. Thus, our results demonstrate that KATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis. 相似文献
76.
77.
Continuous measurement of fluid mobilization from ICF space following acute dehydration by dialyzation in dogs 总被引:1,自引:0,他引:1
The changes of the distribution of body fluid following acute isotonic dialyzation were studied from the results of continuous monitoring of extracellular fluid volume and physiological parameters. An indicator of extracellular space, 51Cr-EDTA, was injected into splenonephrectomized dogs. After the equilibrium of tracer dilution was attained, 10 ml/kg of plasma water was isotonically withdrawn by means of a dialyzer of hollow fiber type. The volumes of extracellular fluid (ECF) and plasma (PV) were continuously monitored for 80 min and plasma osmolality was measured at 10 min intervals. At the 50-60th min after the fluid modification, the reduction of PV was only 3.8 ml/kg and that of ECF was 4.2 ml/kg. The continuous profile of ECF change showed a significant mobilization of water from intracellular fluid (ICF) soon after the dialyzation. It is concluded that, in the state of hypovolemia, plasma fluid is replenished with the transvascular fluid absorption from interstitial space and that, concomitantly, the reduction of ISF is restituted with the fluid mobilization from ICF into extracellular space within the early stage of 1 hr. Good linear correlation was found between the amount of mobilized water from ICF and the increment of plasma osmolality. An increase in osmotic force was considered the mechanism which caused the fluid shift. These findings suggest that the change in plasma osmolality is a good predictor of mobilized volume from ICF in hypovolemia. The effects of inverse fluid modification, i.e., isotonic infusion, were also compared. 相似文献
78.
Kitaichi N Kotake S Morohashi T Onoé K Ohno S Taylor AW 《Journal of leukocyte biology》2002,72(6):1117-1121
To evaluate the potential role of NK1.1 (CD161c) cells in autoimmune uveoretinitis, we treated experimental autoimmune uveoretinitis (EAU)-susceptible mice with anti-CD161c antibodies (PK136) to deplete natural killer (NK) cells. Injection of anti-CD161c antibodies deleted NK cells from the peripheral blood of EAU-susceptible mice. The T cell proliferative response against the ocular autoantigen K2 was not suppressed in mice treated with anti-CD161c antibody when compared with T cells from control mice. Although mice treated with anti-CD161c developed EAU, the clinical severity on days 17 and 19 after induction of EAU was significantly mild in anti-CD161c-treated mice compared with control mice. In addition, the histopathological severity of EAU was significantly milder in mice treated with anti-CD161c antibodies than controls 21 days after induction of EAU. Our results indicate that the severity of EAU is augmented by NK1.1(+) NK cells. 相似文献
79.
Development of a 5' fluorogenic nuclease-based real-time PCR assay for quantitative detection of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis 总被引:1,自引:0,他引:1
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Yoshida A Suzuki N Nakano Y Oho T Kawada M Koga T 《Journal of clinical microbiology》2003,41(2):863-866
A 5' nuclease TaqMan PCR was developed for the quantitative detection of the periodontopathic bacteria Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. The relative numbers of bacteria were measured by the comparative threshold cycle method. This simplified method is a way of obtaining the relative quantities of these organisms from specimens and of monitoring the effect of therapy. 相似文献
80.
Owada-Makabe K Tsubota Y Yukawa K Kakimoto N Liang XM Ichinose M Maeda M 《Neuroscience letters》2005,378(1):18-21
Attempts at protein transduction into specific restricted brain areas have remained unsuccessful. We attempted targeted, direct in vivo protein transduction by microinjecting beta-galactosidase (beta-gal) with hemagglutinating virus of Japan envelope (HVJ-E) vector into the rat nucleus tractus solitarius (NTS). The medulla oblongata including the NTS was removed 6h post-injection and cryostat sections were histochemically stained to detect beta-gal enzymatic activity. beta-gal-positive cells were present in these sections as was beta-gal activity determined by colorimetric analysis. beta-gal-positive cells were not present in the rats microinjected only beta-gal protein without HVJ-E vector. Our findings suggest that direct in vivo protein transduction into specific restricted brain areas is possible. The type of targeted delivery system we present may have wide applications in the administration of therapeutic proteins to the central nervous system. 相似文献