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81.
苏娟 《微生物学免疫学进展》2015,(2):57-61
肉毒毒素是肉毒梭状芽胞杆菌生长繁殖过程中产生的一种细菌外毒素。它可以通过抑制相关神经递质的释放而抑制神经的生理作用,目前临床适应症涉及神经内科、整形外科、康复科、泌尿科等多领域。最新研究发现,肉毒毒素作为毒蕈碱受体拮抗剂可抑制迷走神经释放乙酰胆碱,从而抑制胃癌的发生与发展。同时发现肉毒毒素可通过阻断去甲肾上腺素等神经递质的释放引起神经性的血管舒张,从而打开肿瘤神经血管网来改善肿瘤的放射和化学治疗的疗效。现就其在肿瘤治疗及其辅助治疗相关领域的研究现状进行了综述。 相似文献
82.
83.
Moon DK Tripathi A Sullivan D Siegler MA Parkin S Posner GH 《Bioorganic & medicinal chemistry letters》2011,21(9):2773-2775
Four 5-carbon-linked trioxane dimer orthoesters (6a-6d) have been prepared in 4 or 5 chemical steps from the natural trioxane artemisinin (1). When administered orally to malaria-infected mice using a single dose of only 6 mg/kg body weight along with 18 mg/kg of mefloquine hydrochloride, trioxane dimer orthoester sulfone 6d completely and safely cured the mice; after 30 days, the cured mice showed no detectable parasitemia, gained at least as much weight as the control mice (no infection), and behaved normally. 相似文献
84.
双歧杆菌预防化疗后肠道菌群失调症的临床研究 总被引:1,自引:0,他引:1
探讨双歧杆菌对乳腺癌患者由于化疗导致肠道菌群失调的预防作用。2010年在我科住院的98例乳腺癌患者,在第一周期化疗后有48例出现肠道菌群失调,发生率为48.9%;在3周后的第二周期化疗前1d予患者口服双歧杆菌(双歧杆菌乳杆菌三联活菌片,一次4片,一日2次),直至化疗后2周,肠道菌群失调例数减少到32例,发生率为32.7%。在前后两周期化疗期间监测血常规,粪便菌群失调检查。治疗周期出现菌群失调比例32.7%明显低于对照周期48.9%(P〈0.05),双歧杆菌对乳腺癌患者化疗导致胃肠菌群失调有预防作用。 相似文献
85.
The effectiveness of an apoptosis-targeting therapy may be limited in tumor cells with defects in apoptosis. Recently, considerable
attention in the field of cancer therapy has been focused on the mammalian rapamycin target (mTOR), inhibition of which results
in autophagic cell death. In our study using multidrug-resistant v-Ha-rastransformed NIH3T3 (Ras-NIH 3T3/Mdr) cells, we demonstrated
that rapamycin-induced cell death may result from 2 different mechanisms. At high rapamycin concentrations (≥ 100 nM), cell
death may occur via an autophagy-dependent pathway, whereas at lower concentrations (≤ 10 nM), cell death may occur after
G1-phase cell cycle arrest. This effect was accompanied by upregulation of p21Cip1 and p27Kip1 expression via an autophagy-independent pathway. We also tested whether inhibition of mTOR with low concentrations of rapamycin
and ectopic Beclin-1 expression would further sensitize multidrug resistance (MDR)-positive cancer cells by upregulating autophagy.
Rapamycin at low concentrations might be insufficient to initiate autophagosome formation in autophagy but Beclin-1 overexpression
triggered additional processes downstream of mTOR during G1 cell cycle arrest by rapamycin. Our findings suggest that these combination strategies targeting autophagic cell death may
yield significant benefits for cancer patients, because lowering rapamycin concentration for cancer treatment minimizes its
side effects in patients undergoing chemotherapy. 相似文献
86.
目的:探讨钙离子拮抗剂拉西地平对高温高湿应激大鼠血管平滑肌细胞内内质网应激相关因子葡萄糖调节蛋白78(glucose-regulated protein of 78kD,GRP78)和C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CAAT/enhancer binding protein homologous protein,CHOP)表达的影响。方法:将60只雄性SD大鼠随机分为对照组、高温高湿组、拉西地平组,每组20只。按实验时间(2w、4w、6w、8w)的不同,各组又分为4个亚组,每个亚组5只大鼠。用颈动脉插管法测定各组大鼠的平均动脉压(MAP);用免疫组织化学法检测GRP78和CHOP的表达水平。结果:①高温高湿各组的MAP随着实验时间的延长呈逐渐递增的趋势,高温高湿4w、6w、8w亚组的MAP均显著高于相应的对照组和拉西地平组(P<0.05)。②随着实验时间的延长,高温高湿组GRP78表达量不断增加,6w达到最大值,8w表达减弱。高温高湿4w、6w、8w亚组GRP78表达量均高于相应对照组和拉西地平组,有显著性差异(P<0.05)。③高温高湿组2w、4w、6w、8w亚组CHOP表达量组间比较有显著性差异(P<0.05),8w亚组表达达到最高值;高温高湿组6w、8w亚组与相应对照组和拉西地平组比较有显著性差异(P<0.05)。结论:高温高湿应激可引起血管平滑肌细胞内质网应激反应,导致GRP78表达及CHOP表达的不对称增加,提示高温高湿应激可引起血管平滑肌细胞的损害;拉西地平可以减轻内质网应激,逆转高温高湿应激所致的血管平滑肌细胞的损伤作用,对血管平滑肌细胞有保护作用。 相似文献
87.
Increased expression of DNA repair genes contributes to the extreme resistance shown by melanoma to conventional DNA-damaging chemotherapeutics. One such chemotherapeutic effective against a range of other cancers, but not melanoma, is cisplatin. The DNA repair protein, ERCC1, is needed to remove cisplatin-induced DNA damage. We have shown that ERCC1 is essential for melanoma growth and resistance to cisplatin in a mouse xenograft model. Untreated xenografts of our transformed Ercc1-proficient melanocyte cell line grew very rapidly as malignant melanoma. Cisplatin treatment caused initial shrinkage of xenografts, but cisplatin-resistant regrowth soon followed. Cells reisolated into culture had twofold elevated levels of ERCC1 compared to both input cells and cells reisolated from untreated xenografts. An isogenic Ercc1-deficient derivative grew equally well in vitro as the Ercc1-proficient melanocyte cell line. However, in xenografts, the Ercc1-deficient melanomas were much slower to establish and were completely cured by just two cisplatin treatments. 相似文献
88.
Antibody-targeted chemotherapy of B-cell lymphoma using calicheamicin conjugated to murine or humanized antibody against CD22 总被引:5,自引:0,他引:5
DiJoseph JF Popplewell A Tickle S Ladyman H Lawson A Kunz A Khandke K Armellino DC Boghaert ER Hamann P Zinkewich-Peotti K Stephens S Weir N Damle NK 《Cancer immunology, immunotherapy : CII》2005,54(1):11-24
Antibody-targeted chemotherapy with immunoconjugates of calicheamicin is a clinically validated strategy in cancer therapy. This study describes the selection of a murine anti-CD22 mAb, m5/44, as a targeting agent, its conjugation to a derivative of calicheamicin (CalichDM) via either acid-labile or acid-stable linkers, the antitumor activity of CalichDM conjugated to m5/44, and its subsequent humanization by CDR grafting. Murine IgG1 mAb m5/44 was selected based on its subnanomolar affinity for CD22 and ability to be internalized into B cells. CalichDM conjugated to m5/44 caused potent growth inhibition of CD22+ human B-cell lymphomas (BCLs) in vitro. The conjugate of m5/44 with an acid-labile linker was more potent than an acid-stable conjugate, a nonbinding conjugate with a similar acid-labile linker, or unconjugated CalichDMH in inhibiting BCL growth. CalichDM conjugated to m5/44 caused regression of established BCL xenografts in nude mice. In contrast, both unconjugated m5/44 and a nonbinding conjugate were ineffective against these xenografts. Based on the potent antitumor activity of m5/44-CalichDM conjugates, m5/44 was humanized by CDR grafting to create g5/44, an IgG4 anti-CD22 antibody. Both m5/44 and g5/44 bound CD22 with subnanomolar affinity. Competitive blocking with previously characterized murine anti-CD22 mAbs suggested that g5/44 recognizes epitope A located within the first N-terminal Ig-like domain of human CD22. Antitumor efficacy of CalichDM conjugated to g5/44 against BCL xenografts was more potent than its murine counterpart. Based on these results, a calicheamicin conjugate of g5/44, CMC-544, was selected for further development as a targeted chemotherapeutic agent for the treatment of B-cell malignancies.Abbreviations AcBut
4-(4-Acetylphenoxy) butanoic acid
- AcPAc
(3-Acetylphenyl) acetic acid
- ATC
Antibody-targeted chemotherapy
- BCL
B-cell lymphoma
- CalichDM
N-Acetyl--calicheamicin dimethyl disulfide derivative(s)
- CalichDMA
CalichDM acid
- CalichDMH
CalichDM hydrazide
- CDR
Complementarity determining region
- NHL
Non-Hodgkins lymphoma
- PBMC
Peripheral blood mononuclear cell
- TAA
Tumor-associated antigen 相似文献
89.
90.
The aim of this study was the development of a veterinary dosage form constituted by injectable biodegradable microspheres
designed for the subcutaneous release of carboplatin, a chemotherapeutic drug. Poly(D,L-lactide) (PDLLA) microspheres were
prepared by an emulsification/spray-drying method, using the drug-to-polymer weight ratios 1∶9 and 1∶5; blank microspheres
(1% w/v) were prepared as a comparison. Microparticles were characterized in terms of morphology, encapsulation efficiency,
and in vitro drug release behavior. In vivo tests were conducted on rats by subcutaneous injection of microsphere aqueous
suspensions. Levels of carboplatin were evaluated both in the skin and in serum. The microparticles obtained had a spherical
shape; particle size ranged from 5 to 7 μm, dependent on drug loading. Microspheres were able to control the in vitro release
of the drug: approximately 90% to 100% of the carboplatin was released over 30 days. In vivo results showed that the microspheres
were able to release high drug amounts locally, and sustained serum levels of drug were also achieved. Based on these results,
carboplatin-loaded PDLLA microspheres may be useful for local delivery of the antineoplastic drug to the tumor, avoiding tumor
recurrence in small animals, and may decrease the formation of distant metastases.
Published: September 20, 2005 相似文献