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61.
Yasuna Kobayashi Ryoko Sakai Naomi Ohshiro Masayuki Ohbayashi Noriko Kohyama Toshinori Yamamoto 《Drug metabolism and disposition》2005,33(5):619-622
Organic anion transporter 2 (Oat2 [SLC22A7]) is a multispecific organic anion transporter. Although several substrates of human Oat2 (hOat2) have been elucidated, a possible involvement of hOat2 in drug interaction is less defined. The purpose of this study was to investigate the interaction of theophylline with erythromycin mediated by hOat2 using a Xenopus laevis oocyte expression system. When expressed in Xenopus oocytes, hOat2 mediated the transport of theophylline and erythromycin. The finding indicates that the two compounds are novel substrates for hOat2. The apparent K(m) values for the uptake of hOat2 that mediated the transport of theophylline and erythromycin were 12.6 muM and 18.5 muM, respectively. The hOat2-mediated uptake of [(14)C]theophylline and [(14)C]erythromycin was cis-inhibited by adding erythromycin and theophylline, respectively. Our present findings suggest that hOat2 may, at least in part, be involved in the theophylline-erythromycin interaction in the human liver. 相似文献
62.
63.
Yuka Takakura Hiroyuki Murai Hirokazu Furuya Hirofumi Ochi Jun-ichi Kira 《Clinical neurology》2005,45(5):346-350
A 74-year-old woman suffered from progressive muscle atrophy and weakness of her arms since she was seventy two years old. Before referral to our department, she was diagnosed as having cervical spondylotic myeloradiculopathy and received spinal fusion. Though spinal decompression was successful, muscle weakness of her upper limbs were progressive even after the surgery. On admission, neurological examinations revealed marked atrophy and weakness of her bilateral upper limbs with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower extremities had normal muscle strength, but fasciculations were seen in her all four limbs. Electrophysiologically, motor nerve conduction velocity was almost normal but the amplitude was remarkably decreased, conduction block was not detected, and electromyography showed neurogenic patterns on her all extremities. Spinal progressive musclar atrophy (SPMA) accompanied with Sj?gren's syndrome was the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her serum, we assumed that anterior horn cells were impaired by an autoimmune mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable improvement on her weakness, and the effect lasted for about three months. This is the first case of SPMA with Sj?gren's syndrome which showed good response to PE and IVIG in the early course of the disease. We considered that some SPMA-like motor neuron syndrome accompanied with autoimmune features may require immunomodulating therapies. 相似文献
64.
Dendritic Cells Coinjected with Tumor Cells Treated with an Anticancer Drug to Induce Tumor Rejection 总被引:1,自引:0,他引:1
Naoya Inoue Seiji Yamasaki Kan Kondo Takatsugu Kan Katsuyoshi Furumoto Masayuki Imamura 《Surgery today》2003,33(4):269-276
Purpose: We examined whether bone marrow-derived dendritic cells (DCs) could induce antitumor immunity when a chemotherapeutic drug
was added.
Methods: CT26 (a murine colon cancer cell line syngeneic with BALB/c) and CT26-bearing mice were treated with mitomycin C (MMC) intraperitoneally
(i.p.). Next, mice immunized with a coinjection of DCs and MMC-treated CT26 (i.p.) were given an intradermal inoculation of
CT26. Finally, CT26-bearing mice were treated with MMC (i.p.) with or without DCs, given peritumorally.
Results: Although the inoculated tumor was not rejected in the control mice, CT26 was rejected in 50% of the mice injected with MMC
alone. Apoptosis was observed in the MMC-treated CT26 cells in vitro and in vivo. Immunization with DCs and apoptotic CT26
cells, but not with apoptotic CT26 alone, gave protection against tumor challenge in 7 of 13 mice. A significantly higher
level of cytotoxic T-cell activity and interferon-γ production was seen in the protected mice. When MMC (i.p.) treatment was
followed by peritumoral DC injection in the CT26-bearing mice, remarkable therapeutic effects were observed.
Conclusion: DCs can collaborate with chemotherapy-induced apoptotic tumor cells and elicit improved antitumor immunity, probably through
the acquisition of tumor-associated antigens from apoptotic tumor cells.
Received: January 7, 2002 / Accepted: September 3, 2002
Acknowledgments. We thank Dr. Kazuo Kinoshita for his useful advice on using flow cytometry. This research was partly supported by the Ministry
of Education, Culture, Sports, Science and Technology (No. 11671160).
Reprint requests to: S. Yamasaki 相似文献
65.
Songji Zhao Yuji Kuge Takafumi Mochizuki Toshiyuki Takahashi Kunihiro Nakada Masayuki Sato Toshiki Takei Nagara Tamaki 《Journal of nuclear medicine》2005,46(4):675-682
The biologic mechanisms involved in the intratumoral heterogeneous distribution of 18F-FDG have not been fully investigated. To clarify factors inducing heterogeneous 18F-FDG distribution, we determined the intratumoral distribution of 18F-FDG by autoradiography (ARG) and compared it with the regional expression levels of glucose transporters Glut-1 and Glut-3 and hexokinase-II (HK-II) in a rat model of malignant tumor. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle (n = 7). Tumor tissues were excised 1 h after the intravenous injection of 18F-FDG and sectioned to obtain 2 adjacent slices for ARG and histochemical studies. The regions of interest (ROIs) were placed on ARG images to cover mainly the central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions. The radioactivity in each ROI was analyzed quantitatively using a computerized imaging analysis system. The expression levels of Glut-1, Glut-3, and HK-II were determined by immunostaining and semiquantitative evaluation. The hypoxia-inducible factor 1 (HIF-1) was also immunostained. RESULTS: ARG images showed that intratumoral 18F-FDG distribution was heterogeneous. The accumulation of 18F-FDG in the CT region was the highest, which was 1.6 and 2.3 times higher than those in the PT and NA regions, respectively (P < 0.001). The expression levels of Glut-1, Glut-3, and HK-II were markedly higher in the CT region (P < 0.001) compared with those in the PT region. The intratumoral distribution of 18F-FDG significantly correlated with the expression levels of Glut-1, Glut-3, and HK-II (r = 0.923, P < 0.001 for Glut-1; r = 0.829, P < 0.001 for Glut-3; and r = 0.764, P < 0.01 for HK-II). The positive staining of HIF-1 was observed in the CT region. CONCLUSION: These results demonstrate that intratumoral 18F-FDG distribution corresponds well to the expression levels of Glut-1, Glut-3, and HK-II. The elevated expression levels of Glut-1, Glut-3, and HK-II, induced by hypoxia (HIF-1), may be contributing factors to the higher 18F-FDG accumulation in the CT region. 相似文献
66.
Effects of nilvadipine on the low- and high-voltage activated Ca2+ currents (LVA and HVA ICa, respectively) were compared with other organic Ca2+ antagonists in acutely dissociated rat hippocampal CA1 pyramidal neurons. The inhibitory effects of nilvadipine, amlodipine and flunarizine on LVA ICa were concentration- and use-dependent. The apparent half-maximum inhibitory concentrations (IC50s) at every 1- and 30-s stimulation were 6.3×10−7 M and 1.8×10−6 M for flunarizine, 1.9×10−6 M and 7.6×10−6 M for nilvadipine, and 4.0×10−6 M and 8.0×10−6 M for amlodipine, respectively. Thus, the strength of the use-dependence was in the sequence of nilvadipine>flunarizine>amlodipine. Nilvadipine also inhibited the HVA ICa in a concentration-dependent manner with an IC50 of 1.5×10−7 M. The hippocampal CA1 neurons were observed to have five pharmacologically distinct HVA Ca2+ channel subtypes consisting of L-, N-, P-, Q- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel current which comprised 34% of the total HVA ICa. On the other hand, amlodipine non-selectively inhibited the HVA Ca2+ channel subtypes. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca2+ influx through both LVA and HVA L-type Ca2+ channels, in combination with the cerebral vasodilatory action, may prevent neuronal damage during ischemia. 相似文献
67.
Atsuhiko Chiba Tatsuo Akema Masayuki Iigo Yuta Nagami Fukuko Kimura Jun-ichi Toyoda 《Journal of neuroendocrinology》1998,10(2):79-84
It has been recently reported that acute immobilization stress almost completely suppresses the luteinizing hormone (LH) release induced by naloxone, a μ-opioid antagonist, in ovariectomized estrogen-primed rats. The present study examined the possible involvement of the pineal gland in the acute immobilization-related suppression of the naloxone-induced LH release. An intraventricular (ICV) injection of 15 μg naloxone produced an abrupt increase in circulating LH concentrations in non-stressed rats. The naloxone-induced LH release was completely eliminated when tested 60 min after the end of a 30 min session of acute immobilization. The same stress conditions did not affect LH-releasing hormone (LHRH)-induced LH release, suggesting that the stress-related suppression of the naloxone-induced LH release was a suprapituitary event. In chronically-pinealectomized rats, but not in sham-pinealectomized rats, naloxone injected 60 min after the end of the stress session evoked a significant increase in serum LH concentrations. However, naloxone injected ICV during the acute immobilization did not elicit LH release in either pinealectomized or sham-operated rats. Under non-stressed conditions, the LH secretory response to naloxone was similar in pinealectomized and sham-operated animals. The same stress (30 min immobilization) significantly increased pineal melatonin content as well as plasma melatonin concentrations in rats bearing intact pineal glands, indicating that stress actually affected the pineal function. These results provide evidence for a role of the pineal in the suppression of the LH response to naloxone after stress, but not during stress. 相似文献
68.
Kaoru Nagahori Jun Itakura Hiroyasu Miura Hidemitsu Sugai Masayuki Yamamoto Yoshiro Matsumoto Takao Ainota Yoshihiro Akahane 《Journal of Hepato-Biliary-Pancreatic Surgery》1995,2(3):288-291
We report a metastatic pulmonary tumor resected by video-assisted thoracoscopic surgery. A 63-year-old female was found to
have four nodules of hepatocellular carcinoma (HCC) in January 1991; after non-surgical treatment, the tumors had become necrotic.
In June 1992, a new HCC nodule was found. After infusion chemotherapy, it became necrotic. In September 1993, a solitary lung
tumor, 2.4 cm in diameter, appeared at the periphery of the right lung. Because the tumor was considered to be a metastatic
HCC rather than a primary lung cancer, it was removed by thoracoscopic wedge resection. Although whether metastasectomy contributes
to prolongation of survival is still controversial, thoracoscopic pulmonary resection may be indicated for solitary peripheral
metastasis, if the primary HCC is well controlled by multidisciplinary treatment. 相似文献
69.
Terashima Y Onai N Murai M Enomoto M Poonpiriya V Hamada T Motomura K Suwa M Ezaki T Haga T Kanegasaki S Matsushima K 《Nature immunology》2005,6(8):827-835
Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration. 相似文献
70.
Nakanishi M Yabe S Tanaka N Ito Y Nakamura KT Kitade Y 《Molecular and biochemical parasitology》2005,143(2):146-151
S-adenosylhomocysteine hydrolase is a prospective target for developing new anti-malarial drugs. Inhibition of the hydrolase results in an anti-cellular effect due to the suppression of adenosylmethionine-dependent transmethylations. Based on the crystal structure of Plasmodium falciparum S-adenosylhomocysteine hydrolase which we have determined recently, we performed mutational analyses on P. falciparum and human enzymes. Cys59 and Ala84 of the parasite enzyme, and the equivalent residues on the human enzyme, Thr60 and Gln85, were examined. Mutations of Cys59 and Thr60 caused dramatic impact on inhibition by 2-fluoronoraristeromycin without significant effect both on its kinetic parameters and on inhibition constant against noraristeromycin. In addition, the impact was independent from the electronegativity of the side chain of the substituting residue. These results showed that steric hindrance between a functional group at the 2-position of an adenine nucleoside inhibitor and Thr60 of the human enzyme, not an electrostatic effect, contributed to inhibitor selectivity. 相似文献