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671.
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Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors 总被引:31,自引:9,他引:22
Rafii S; Shapiro F; Pettengell R; Ferris B; Nachman RL; Moore MA; Asch AS 《Blood》1995,86(9):3353-3363
Endothelial cells are a major component of the bone marrow (BM) microenvironment that regulate the trafficking and homing of hematopoietic progenitor and stem cells. In this paper, we provide evidence that BM endothelial cells (BMECs) also support multilineage hematopoiesis by elaboration of soluble cytokines. Hematopoietic progenitor cells incubated in direct contact with BMEC monolayers, or physically separated by microporous membrane, expanded five-fold to sevenfold at 7 days, in the absence of exogenous cytokines. Flow cytometric analysis of proliferating progenitor cells grown in the presence of BMEC monolayers showed that by day 14 of coculture, 70% to 80% of hematopoietic cells were myeloid, expressing CD15 or CD14, and 14% to 19% were megakaryocytic, expressing GPIIb/IIIa or GPIb. CD34+ cells derived from umbilical cord blood, cultured in the upper chamber of transwell culture plates, as well as the cells grown in direct contact with BMEC monolayers, generated progenitors for up to 70 days. Unstimulated BMEC monolayers constitutively produce interleukin-6, Kit- ligand, granulocyte colony-stimulating factor, and granulocyte macrophage colony-stimulating factor. These data suggest that BMEC regulate proliferation of hematopoietic progenitor cells and long-term culture initiating cells by elaboration of lineage-specific cytokines. 相似文献
673.
Curative and palliative radiotherapy of bladder cancer. A retrospective study of 11 years experience
A total of 119 patients with bladder cancer were irradiated over a period of 11 years. Fifteen had Stage B1, 15 B2, 38 C, 9 D1, 23 D2, and 19 D3. The pelvis, bladder, or both received less than or equal to 7,000 rad (70 Gy) in 7 weeks in 78 patients treated with curative intent (Group I) and less than or equal to 5,000 rad (50 Gy) in 5 weeks in 41 patients treated for palliation (Group II). Major complications developed in 3 patients due to irradiation and were fatal in 2, while 22 had minor, self-limited complications which were often related to the technique used. In Group I, the 3- and 5-year disease-free survival rates were 18% and 14%, respectively, whereas only 3% of Group II patients survived 3 years; however, reasonable palliation was achieved in a large percentage of cases. Superficial lesions (B1) can be cured with irradiation (60% 5-year survival). Other prognostic factors are presented. 相似文献
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The term embryonic gene is discussed in which an operational definition is given, namely that it be restricted for those genes which are active during the embryonic state but repressed during differentiation. After generalizing a large variety of different types of carcinogenic agents and their action, which in principle are capable of activating embryonic genes, a preliminary notion of the carcinogenic process was derived. It appears that the bioalkylation pattern can be perturbed by a variety of agents from electromagnetic radiation to ethionine. Specific genes or their corresponding repressors such as an embryonic type phospho-protein kinase would become derepressed because of their methylation status (or by some other analogous alteration, e.g., via a specific mutation of a proto-oncogene that would create an embryonic type kinase, DNA intercalation by planar molecules, or, a hereditary process such as V-type position effect). This would cause competent stem type precursor cells containing easily derepressed or partially repressed arrays of embryonic genes to become activated, producing many features characteristic of a neoplastic cell. 相似文献
676.
Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances 总被引:1,自引:0,他引:1
MacCarty RL; LaRusso NF; May GR; Bender CE; Wiesner RH; King JE; Coffey RJ 《Radiology》1985,156(1):43-46
Cholangiograms from 104 patients (and serial cholangiograms in 66 patients) with primary sclerosing cholangitis (PSC) were reviewed. In 13 patients the additional diagnosis of cholangiocarcinoma was made at biopsy or autopsy. Cholangiograms from patients with both PSC and carcinoma were compared with cholangiograms from patients with PSC alone. Marked dilatation of ducts or ductal segments (100% vs. 24%) and the appearance of a polypoid mass (46% vs. 7%) were common findings in the group of patients whose disease was complicated by malignancy. In the malignant group, polypoid masses were larger, measuring 1 cm or greater in diameter. On serial cholangiograms, four of 15 patients with progressive stricture formation and four of five with progressive ductal dilatation proved to have carcinomas. The frequent occurrence of bile duct carcinoma as a complication of PSC in this group of patients indicates that PSC has a strong tendency to undergo malignant degeneration. Cholangiographic findings which suggest malignant degeneration include markedly dilated ducts or ductal segments, presence of a polypoid mass 1 cm or greater in diameter, and progressive stricture formation or ductal dilatation. 相似文献
677.
Interleukin-6 promotes multiple myeloma cell growth via phosphorylation of retinoblastoma protein 总被引:5,自引:2,他引:3
Urashima M; Ogata A; Chauhan D; Vidriales MB; Teoh G; Hoshi Y; Schlossman RL; DeCaprio JA; Anderson KC 《Blood》1996,88(6):2219-2227
Interleukin-6 (IL-6) mediates autocrine and paracrine growth of multiple myeloma (MM) cells and inhibits tumor cell apoptosis. Abnormalities of retinoblastoma protein (pRB) and mutations of RB gene have been reported in up to 70% of MM patients and 80% of MM-derived cell lines. Because dephosphorylated (activated) pRB blocks transition from G1 to S phase of the cell cycle whereas phosphorylated (inactivated) pRB releases this growth arrest, we characterized the role of pRB in IL-6-mediated MM cell growth. Both phosphorylated and dephosphorylated pRB were expressed in all serum-starved MM patient cells and MM-derived cell lines, but pRB was predominantly in its phosphorylated form. In MM cells that proliferated in response to IL-6, exogenous IL-6 downregulated dephosphorylated pRB and decreased dephosphorylated pRB-E2F complexes. Importantly, culture of MM cells with RB antisense, but not RB sense, oligonucleotide (ODN) triggered IL- 6 secretion and proliferation in MM cells; however, proliferation was only partially inhibited by neutralizing anti-IL-6 monoclonal antibody (MoAb). In contrast to MM cells, normal splenic B cells express dephosphorylated pRB. Although CD40 ligand (CD40L) triggers a shift from dephosphorylated to phosphorylated pRB and proliferation of B cells, the addition of exogenous IL-6 to CD40L-treated B cells does not alter either pRB or proliferation, as observed in MM cells. These results suggest that phosphorylated pRB is constitutively expressed in MM cells and that IL-6 further shifts pRB from its dephosphorylated to its phosphorylated form, thereby promoting MM cell growth via two mechanisms; by decreasing the amount of E2F bound by dephosphorylated pRB due to reduced dephosphorylated pRB, thereby releasing growth arrest; and by upregulating IL-6 secretion by MM cells and related IL-6- mediated autocrine tumor cell growth. 相似文献
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