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21.
22.
Murine sarcoma viruses: the helper-independence reported for a Moloney variant is unconfirmed; distinct strains differ in the size of their RNAs. 总被引:21,自引:0,他引:21
A variant of Moloney murine sarcoma virus (Mo-MSV) reported to behave like a nondefective sarcoma virus was subjected to biological and biochemical analyses to determine whether its alleged helper-independence could be confirmed. When plated at low multiplicity the virus was shown to readily generate (four out of six) transformed clones which failed to produce virus unless superinfected with helper leukemia virus. The RNA of the parental virus stock was compared electrophoretically to that from clones which produced virus after the initial infection (producer clones) or after superinfection with Mo-murine leukemia virus (MLV) (nonproducer clones). All clones contained a MSV-specific 30 S RNA species. In addition, virus from one producer clone also contained 38 S MLV RNA at a high relative concentration, indicating that the original Mo-MSV stock must have contained such an RNA species. However, the original virus stock as well as virus from another producer clone contained 38 S MLV RNA at a low, uncertain relative concentration. A hypothesis consistent with these and previous data suggests that the Mo-MSV variant investigated here is defective and contains helper leukemia virus at a low concentration. This explains (i) the ready generation of nonproducer clones by infection at low multiplicity, (ii) the difficulty in detecting helper leukemia virus 38 S RNA in the original virus stock, and (iii) the low complexity (approximately 1.9 × 106 daltons) of the MSV-specific 30 S RNA. These results are compatible with the properties reported for a defective MSV genome, but incompatible with those of a nondefective MSV genome. The MSV-specific RNA components of different clonal isolates of Mo-MSV differed from each other in size, ranging between 2.1 and 1.6 × 106. The Harvey sarcoma virus-specific RNA was 1.9 × 106, that of Kirsten sarcoma virus was 2.5 × 106, and the spleen focus forming component of Friend virus was 2.0 × 106. The sarcoma- or transformation-specific RNA components of all transforming viruses tested here were smaller than the 38 S RNA of helper leukemia viruses of 3.1 × 106. 相似文献
23.
The vascular lesions in vascular and mixed dementia: the weight of functional neuroanatomy 总被引:6,自引:0,他引:6
Zekry D Duyckaerts C Belmin J Geoffre C Herrmann F Moulias R Hauw JJ 《Neurobiology of aging》2003,24(2):213-219
Vascular dementia appears rarer than previously thought, but the contribution of vascular lesions to cognitive impairment in Alzheimer's disease (AD) affected patients (mixed dementias) is now recognized as frequent. The role of strategic areas of the brain involved in the cognitive decline induced by vascular lesions and their relative contributions to the severity of the dementing process remain poorly understood. We determined the relationship between the severity of clinical dementia and the volume of different brain areas affected by infarcts in a prospective clinicopathological study in elderly patients. A volumetric study of the functional zones of Mesulam's human brain map affected by vascular lesions was made and correlations between quantified neuropathological data and the severity of dementia were performed in cases with large vascular lesions only, pure AD, and both lesions. The severity of cognitive impairment was significantly correlated with the total volume of infarcts but in a multi-variate model the volume destroyed in the limbic and heteromodal association areas, including the frontal cortex and in the white matter explained 50% of the variability in MMSE and GDS. The total volume of ischemic lesions explained only 0.1-5% of the variability in MMSE and GDS. Age only explained an extra of 0.1-1.6%. This study confirms that infarcts located in strategic areas have a role in the mechanism of cognitive impairment and brings a key for their quantification. It may be useful for developing neuropathological criteria in multi-infarct and mixed dementias. 相似文献
24.
Dina Marek‐Yagel Yoav Bolkier Ortal Barel Amir Vardi David Mishali Uriel Katz Yishay Salem Shachar Abudi Omri Nayshool Nitzan Kol Annick Raas‐Rothschild Gideon Rechavi Yair Anikster Ben Pode‐Shakked 《American journal of medical genetics. Part A》2020,182(5):987-993
The genetic basis of congenital heart malformations associated with disruption of left–right (L–R) asymmetry is broad and heterogenous, with variants in over 25 genes implicated thus far. Of these, deleterious variants in the Growth/Differentiation Factor 1 (GDF1) gene have been shown to cause heterotaxy with varied complex heart malformations of left–right patterning, in 23 individuals reported to date, either in monoallelic or biallelic state. We report three unrelated individuals exhibiting right isomerism with congenital heart defects, each originating from a consanguineous kindred of Arab‐Muslim descent. Using whole exome sequencing, a shared novel homozygous truncating c.608G > A (p.W203*) variant in the GDF1 gene was revealed as the molecular basis of their disease. Subsequently, targeted sequencing of this variant showed full segregation with the disease in these families, with a total of over 15 reportedly affected individuals, enabling genetic counseling, prenatal diagnosis, and planning of future pregnancies. Our findings further confirm the association of biallelic GDF1 variants, heterotaxy and congenital heart defects of left–right patterning, and expand the previously described phenotypic spectrum and mutational profile. Moreover, we suggest targeted screening for the p.W203* variant in relevant clinical circumstances. 相似文献
25.
Zohreh Talebi-Yazdabadi Neda Jahanbakhsh Kianoush Dormiani Mahboobeh Forouzanfar Liana Lachinani Dina Zohrabi Marziyeh Tavalaee Mohammad Hossein Nasr-Esfahani 《Andrologia》2021,53(10):e14187
MUSASHI (MSI) family plays the main role in the spermatogenesis process. The purpose of this study was the assessment of sperm MSI1 and MSI2, and sperm functional tests in infertile men (n = 30) with varicocele and fertile men (n = 30). Furthermore, MSI1 and MSI2 proteins were assessed in testicular tissue of azoospermic men (n = 9) as well as epididymal spermatozoa and testis of mice. Expression of MSI1 and MSI2 was assessed at RNA and protein levels in human spermatozoa. Sperm concentration and motility were significantly lower, while abnormal sperm morphology, lipid peroxidation, DNA fragmentation and protamine deficiency were significantly higher in men with varicocele compared to fertile individuals. Any significant difference was not observed in the expression of MSI1 and MSI2 mRNA between the two groups. Unlike MSI1 protein that was not detectable in humans, the relative expression of MSI2 protein was similar in varicocele and fertile individuals. The expression level of both Msi1 and Msi2 proteins was also observable in mouse spermatozoa. No significant relationship was observed between sperm functional parameters with expression of these genes. The data of this study demonstrated that although MSI1 and MSI2 play important roles during spermatogenesis, their relative expression in spermatozoa was not affected by varicocele. 相似文献
26.
Dina Chelouche Lev Amir Onn Vladislava O Melinkova Claudia Miller Valerie Stone Maribelis Ruiz Eric C McGary Honnavara N Ananthaswamy Janet E Price Menashe Bar-Eli 《Journal of clinical oncology》2004,22(11):2092-2100
PURPOSE: In recent years, the incidence of cutaneous melanoma has increased more than that of any other cancer. Dacarbazine is considered the gold standard for treatment, having a response rate of 15% to 20%, but most responses are not sustained. Previously, we have shown that short exposure of primary cutaneous melanoma cells to dacarbazine resulted in the upregulation of interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The purpose of the present study was to determine how long-term exposure of melanoma cells to dacarbazine would affect their tumorigenic and metastatic potential in vivo. MATERIALS AND METHODS: The primary cutaneous melanoma cell lines SB2 and MeWo were repeatedly exposed in vitro to increasing concentrations of dacarbazine, and dacarbazine-resistant cell lines SB2-D and MeWo-D were selected and examined for their ability to grow and metastasize in nude mice. RESULTS: The dacarbazine-resistant cell lines SB2-D and MeWo-D exhibited increased tumor growth and metastatic behavior in vivo. This increase could be explained by the activation of RAF, MEK, and ERK, which led to the upregulation of IL-8 and VEGF. More IL-8, VEGF, matrix metalloproteinase-2 (MMP-2), and microvessel density (CD-31) were found in tumors produced by SB2-D and MeWo-D in vivo than in those produced by their parental counterparts. No mutations were observed in BRAF. CONCLUSION: Our results have significant clinical implications. Treatment of melanoma patients with dacarbazine could select for a more aggressive melanoma phenotype. We propose that combination treatment with anti-VEGF/IL-8 or MEK inhibitors may potentiate the therapeutic effects of dacarbazine. 相似文献
27.
Alberto Gabizon Aviva T Horowitz Dorit Goren Dina Tzemach Hilary Shmeeda Samuel Zalipsky 《Clinical cancer research》2003,9(17):6551-6559
PURPOSE: To compare the in vivo tissue distribution of folate-targeted liposomes (FTLs) injected i.v. in mice bearing folate receptor (FR)-overexpressing tumors (mouse M109 and human KB carcinomas, and mouse J6456 lymphoma) to that of nontargeted liposomes (NTLs) of similar composition. EXPERIMENTAL DESIGN: A small fraction of a folate-polyethylene-glycol (PEG)-distearoyl-phosphatidylethanolamine conjugate was incorporated in FTLs. Both FTLs and NTLs were PEGylated with a PEG-distearoyl-phosphatidylethanolamine conjugate to prolong circulation time. Liposomes were labeled with [(3)H]cholesterol hexadecyl ether with or without doxorubicin loading. Liposome levels in plasma, tissues, or ascites were assessed by the number of [(3)H] counts. For doxorubicin-loaded formulations, we also determined the tissue doxorubicin levels by fluorimetry. To estimate the amount of liposomes directly associated with tumor cells in vivo, we determined the [(3)H]radiolabel counts in washed pellets of ascitic tumor cells using the ascitic J6456 lymphoma RESULTS: FTLs retained the folate ligand in vivo, as demonstrated by their ability to bind ex vivo to FR-expressing cells after prolonged circulation and extravasation into malignant ascitic fluid. In comparison with NTLs, FTLs were cleared faster from circulation as a result of greater liver uptake. Despite the lower plasma levels, tumor levels of FTL-injected mice were not significantly different from those of NTL-injected mice. When NTLs and FTLs were loaded with doxorubicin, liver uptake decreased because of liver blockade, and uptake by spleen and tumor increased. When tumor-to-tissue liposome uptake ratios were analyzed, the targeting profile of FTLs was characterized by higher tumor:skin, and tumor:kidney ratios but lower tumor:liver ratio than NTLs. After a concomitant dose of free folic acid, FTLs (but not NTLs) plasma clearance and liver uptake were inhibited, indicating that accelerated clearance was mediated by the folate ligand. Surprisingly tumor uptake was not significantly affected by a codose of folic acid. In the J6456 ascitic tumor model, tumor cell-associated liposome levels were significantly greater for FTL-injected mice than for NTL-injected mice, despite slightly higher levels of the latter in whole ascites. CONCLUSIONS: Whereas folate targeting does not enhance overall liposome deposition in tumors, the targeting profile of tumor versus other tissues is substantially different and intratumor liposome distribution in ascitic tumors is affected favorably with a selective shift toward liposome association with FR-expressing cells. 相似文献
28.
A fully human antimelanoma cellular adhesion molecule/MUC18 antibody inhibits spontaneous pulmonary metastasis of osteosarcoma cells in vivo. 总被引:6,自引:0,他引:6
Eric C McGary Amy Heimberger Lisa Mills Kristy Weber Gary W Thomas Mikhail Shtivelband Dina Chelouche Lev Menashe Bar-Eli 《Clinical cancer research》2003,9(17):6560-6566
PURPOSE: The melanoma cellular adhesion molecule, also known as MUC18, is highly expressed on several tumors, including bone sarcomas. The level of MUC18 expression has been found to correlate directly with tumor progression and metastatic potential. These observations have established MUC18 as a candidate mediator of tumor growth and metastasis, and suggest that blockade of MUC18 might be a potential target for immunotherapy against several MUC18-expressing tumors, including human bone sarcomas. EXPERIMENTAL DESIGN: To investigate whether blockade of MUC18 might be a potential target for immunotherapy against osteosarcoma, we have recently developed a fully human anti-MUC18 antibody, ABX-MA1. We studied the effect of ABX-MA1 on growth, adhesion, invasion, and metastasis of human osteosaroma cells both in vitro and in vivo. RESULTS: MUC18 was widely expressed on both osteosarcoma and Ewing's sarcoma cells. ABX-MA1 had no effect on the proliferation of osteosarcoma cells in vitro, nor did it significantly inhibit the growth of KRIB human osteosarcoma cells when they were orthotopically implanted into the tibias of nude mice. However, after 6 weeks, significantly fewer ABX-MA1-treated mice developed spontaneous pulmonary metastases than did IgG-treated control mice. Additionally, ABX-MA1 decreased the invasion of osteosarcoma cells through Matrigel-coated filters and disrupted homotypic adhesion between osteosarcoma cells and their heterotypic interaction with human vascular endothelial cells. CONCLUSIONS: Our findings demonstrate that MUC18 plays a central role in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by ABX-MA1 may be a novel immunotherapeutic approach in the management of this tumor. 相似文献
29.
Large Scale Manufacturing of B43(Anti-CD19)-Genistein for Clinical Trials in Leukemia and Lymphoma 总被引:1,自引:0,他引:1
Dorothea E. Myers Andrew Sicheneder Dina Clementson Nancy Dvorak Taracad Venkatachalam Alexander Rostov Sev Mridula Chandan-Langlie Fatih M. Uckun 《Leukemia & lymphoma》1998,29(3):329-338
We have conjugated the murine monoclonal anti-CD 19 antibody B43 to the tyrosine kinase inhibitor genistein to construct an effective immunoconjugate against CD 19 antigen positive hematologic malignancies. The scaled-up production and purification of B43 antibody, genistein, and B43-Genistein immunoconjugate permitted the manufacturing of a highly purified clinical-grade B43-Genistein preparation. In clonogenic assays, B43-Genistein elicited selective and potent cytotoxicity against CD 19 antigen positive human leukemia cells. To our knowledge, this work represents the first effort of producing a clinical-grade genistein immunoconjugate for treatment of B-lineage leukemia and lymphoma. 相似文献
30.
Elena V. Suntsova Alexey A. Maschan Dina D. Baydildina Irina I. Kalinina Uliana N. Petrova Alexey V. Pshonkin Galina A. Novichkova 《Pediatric blood & cancer》2019,66(6)
We retrospectively analyzed sequential therapy with romiplostim and eltrombopag in 23 children with immune thrombocytopenia: switching from romiplostim to eltrombopag (10 patients) or vice versa (13 patients). The median age of patients at enrollment in the study was 5.6 years (2‐15 years). Switching from romiplostim to eltrombopag was effective in eight (80%) patients, whereas switching from eltrombopag to romiplostim was effective in eight (62%) patients. The response rate was similar in patients failing the first thrombopoietin receptor agonist and those who had previous response. To date, all responders continue to maintain platelets over 50 × 109/L at 13‐39 months after switching. 相似文献