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71.
Localization of putative tumor suppressor loci by genome-wide allelotyping in human pancreatic endocrine tumors 总被引:1,自引:0,他引:1
DC Chung SB Brown F Graeme-Cook LG Tillotson AL Warshaw RT Jensen A Arnold 《Canadian Metallurgical Quarterly》1998,58(16):3706-3711
Only two tumor suppressor gene loci, one on 3p25 and the MEN1 gene on 11q13, have thus far been implicated in the pathogenesis of sporadic human pancreatic endocrine tumors (PETs). A genome-wide allelotyping study of 28 human PETs was undertaken to identify other potential tumor suppressor gene loci. In addition to those on chromosomes 3p and 11q, frequent allelic deletions were identified on 3q (32%), 11p (36%), 16p (36%), and 22q (29%). Finer deletion mapping studies localized the smallest regions of common deletion to 3q27, 11p13, and 16p12.3-13.11. Potential candidate genes at these loci include WT1 (11p13), TSC2 (16p13), and NF2 (22q12), but no known tumor suppressor gene localizes to 3q27. The mean fractional allelic loss among these human PETs is 0.126, and no correlation was observed between allelic loss and clinical parameters, including age, sex, hormonal subtype, and disease stage. These findings highlight novel locations of tumor suppressor gene loci that contribute to the pathogenesis of human PETs, and several of these on 3p, 3q, and 22q are syntenic with loci on mouse chromosomes 9 and 16 that are implicated in a murine transgenic model of PETs. 相似文献
72.
PS Frenette S Subbarao IB Mazo UH von Andrian DD Wagner 《Canadian Metallurgical Quarterly》1998,95(24):14423-14428
The adhesive mechanisms allowing hematopoietic progenitor cells (HPC) homing to the bone marrow (BM) after BM transplantation are poorly understood. We investigated the role of endothelial selectins and vascular cell adhesion molecule-1 (VCAM-1) in this process. Lethally irradiated recipient mice deficient in both P-and E-selectins (P/E-/-), reconstituted with minimal numbers (=5 x 10(4)) of wild-type BM cells, poorly survived the procedure compared with wild-type recipients. Excess mortality in P/E-/- mice, after a lethal dose of irradiation, was likely caused by a defect of HPC homing. Indeed, we observed that the recruitment of HPC to the BM was reduced in P/E-/- animals, either splenectomized or spleen-intact. Homing into the BM of P/E-/- recipient mice was further compromised when a function-blocking VCAM-1 antibody was administered. Circulating HPC, 14 hr after transplantation, were greatly increased in P/E-/- mice treated with anti-VCAM-1 compared with P/E-/- mice treated with just IgG or wild-type mice treated with either anti-VCAM-1 or IgG. Our results indicate that endothelial selectins play an important role in HPC homing to the BM. Optimal recruitment of HPC after lethal doses of irradiation requires the combined action of both selectins and VCAM-1 expressed on endothelium of the BM. 相似文献
73.
AA Bialasiewicz JX Ma U Schandig D von Domarus G Richard 《Canadian Metallurgical Quarterly》1998,213(5):262-270
BACKGROUND: Tumor necrosis may reflect a destructive immune reaction. Systematic and statistically significant comparative clinico-histopathologic studies have not yet been reported. PATIENTS AND METHODS: 113 necrotizing choroidal melanomas (NCM) recruited from 701 enucleated globes 1967-1988 were resectioned, stained and compared to 100 choroidal melanomas without necrosis (CM), and data of 74 patients with a follow-up of more than 10 years were evaluated. RESULTS: Statistically significant characteristics of NCM were: patient age < 60 yrs. for NCM 27.4%, CM 46%; patient age in men for NCM was 64 yrs on average (CM: 58 yrs.), in women for NCM 67 yrs. (CM: 59 yrs.). Time elapsed between first symptoms and enucleation was < 12 months in 15.9% of NCM (89% for CM), and > 12 months in 23.9% of NCM (11% in CM). Mixed or epitheloid cell tumors was seen in 54.9% of NCM and 49% of CM, spindle cell tumors in 36.3% of NCM and 51% in CM. Advanced tumor stages T3 and T4 were present in 45.1% resp. 36.3% of NCM compared to 37% resp. 16% in CM. Scleral invasion was documented in 67.3% of NCM and 37% of CM, extrascleral dissemination in 43% of NCM and 16% of CM. Secondary glaucomas were seen in 62.2% of NCM and 6% CM, a penetration through Bruch's membrane in 61.0% of NCM and 46% of CM. Intratumoral hemorrhage was noted in 68.14% of NCM and 24% of CM, extratumoral bleeding in 23.9% of NCM and 0% CM. Inflammatory reactions in tumors were observed in 96.7% of NCM harboring > 30% necrosis compared to 5% in CM, and extratumoral in 94.5% of NCM and 0% of CM. Intraocular extratumoral necrosis was seen in 23.9% of NCM and 0% of CM. There were no significant differences in the degree of pigmentation of the 90.3% pigmented NCM or of the 94% pigmented CM, neither in the tumor localization, being constantly behind the equator in 87% of cases. Survival of patients with NCM patients was 5 years and 9 months on average (5-year mortality rate 41.9%), and 74.3% were deceased from metastatic spread. CONCLUSIONS: Significant clinical and histopathological differences between necrotizing and non-necrotizing malignant melanomas of the choroid can be identified. The inflammatory reaction of NCM must be further elucidated, particularly with respect to the nature of tumor-infiltrating lymphocytes. 相似文献
74.
DJ Schurman A Matityahu SB Goodman W Maloney S Woolson H Shi DA Bloch 《Canadian Metallurgical Quarterly》1998,(353):175-184
Postoperative knee flexion in patients undergoing Insall-Burstein-II total knee arthroplasty at 2 years was evaluated regarding two basic questions: what groups of patients gain or lose the most flexion and what groups of patients have the best or worst postoperative flexion. Thirteen preoperative variables (maximum flexion, flexion arc, tibiofemoral angle, quadriceps strength, extensor lag, Knee Society score, Knee Society patient assessment, gender, age, height, weight, diagnosis, and surgeon) and four postoperative variable (leg length change, tibiofemoral angle, distance from patella to the joint line, and the tibial prosthesis anteroposterior translation on a lateral radiograph) were used in an attempt to explain postoperative flexion. The analysis was performed on 164 consecutive Insall-Burstein-II total knees in which the data were gathered prospectively on a time oriented medical record database. A regression tree analysis was used to identify several groups of patients, characterized by preoperative factor values, who had markedly above average performance on postoperative flexion. The preoperative factors identified include preoperative flexion, flexion arc, tibiofemoral angle, extensor lag, diagnosis, and age. The only postoperative variable of significance was tibiofemoral angle. Among the potential determinants of postoperative flexion that failed to appear predictive were the Knee Society scores and surgeon. Preoperative flexion is known to be a critical determinant of postoperative flexion in total knee replacement. However, in the current study, preoperative flexion accounted for only half of the difference between the best (122 degrees) and the worst (88 degrees) group, as determined with regression tree analysis. 相似文献
75.
Prostaglandins act through specific receptors to stimulate cyclic AMP formation which inhibits platelet activation and relaxes vascular smooth muscle. We have used RT-PCR combined with Southern blot analysis to determine the subtypes of prostaglandin receptor on platelets. Platelets expressed the EP4 rather than the EP2 prostaglandin EP receptor subtype, whereas vascular smooth muscle cells predominantly expressed the EP2 receptor. The IP receptor, which binds prostacyclin and couples to stimulation of adenylyl cyclase, and three isoforms of the inhibitory EP3 receptor were equally expressed in platelets, HEL cells and umbilical artery smooth muscle cells. The EP3-II isoform showed variation in level of expression among the three cell types. As a positive control for the presence of platelet RNA, PCR was performed using primers specific for the alpha chain of the platelet membrane glycoprotein Ib. As a negative control for the absence of T and B cell contamination in the platelet RNA, PCR was performed using primers specific for the cell specific cluster determinants CD2 (a T-cell marker) and CD20 (a B-cell marker). The finding that platelets express both stimulatory and inhibitory prostaglandin receptors provides confirmation of a homeostatic model of regulation of platelet adenylyl cyclase previously proposed. 相似文献
76.
GF Makhaeva IV Filonenko VL Yankovskaya SB Fomicheva VV Malygin 《Canadian Metallurgical Quarterly》1998,19(4-5):623-628
Acetylcholinesterase (AChE) and neuropathy target esterase (neurotoxic esterase, NTE) are two major target enzymes for organophosphorus (OP) esters. The relative potency of an OP ester to react with AChE or with NTE in vitro correlates with its relative potency in vivo to cause acute toxicity (death) or organopohosphate-induced delayed neurotoxicity (OPIDN). On this basis extrapolation from in vitro to in vivo data now seems justifiable to predict risk of OPIDN. The kinetics of NTE and AChE inhibition by experimental pesticides of the general formula (RO)2P(O)ON=CClCH2Cl, where R = methyl, ethyl, isopropyl, propyl, isobutyl, butyl, pentyl, has been studied. Compounds with short R (methyl, ethyl) were shown to be far more potent inhibitors of AChE than NTE. Both anti-NTE activity, selectivity for NTE and, correspondingly, the propensity of compounds to cause OPIDN rise with increasing their hydrophobicity. A high value of ki(NTE)/ki(AChE) for R = pentyl suggests that this compound would have the potential to cause OPIDN at doses lower than the LD50. A quantitative structure-activity relationships (QSAR) analysis indicated that NTE and AChE have different structural and electronic requirements for their respective OP inhibitors. 相似文献
77.
Bowen's disease has a particular predilection for the lower leg, especially in women. A review of the literature for treating Bowen's disease is presented and the problems associated with treating the lower leg emphasized. Evidence for the various treatment modalities used to treat Bowen's disease largely comes from studies that lack good methodology in terms of standardized techniques, patient controls and adequate follow-up. In particular the widely accepted recommendation for excision is not supported by evidence that this treatment is superior to other modalities. The choice of treatment for Bowen's disease should take into account the patient's general condition, the site and size of the lesion. 相似文献
78.
79.
AR Zuberi GJ Christianson SB Dave JA Bradley DC Roopenian 《Canadian Metallurgical Quarterly》1998,161(2):821-828
The H3 complex, on mouse Chromosome 2, is an important model locus for understanding mechanisms underlying non-self Ag recognition during tissue transplantation rejection between MHC-matched mouse strains. H3a is a minor histocompatibility Ag gene, located within H3, that encodes a polymorphic peptide alloantigen recognized by cytolytic T cells. Other genes within the complex include beta2-microglobulin and H3b. A yeast artificial chromosome (YAC) contig is described that spans the interval between D2Mit444 and D2Mit17, a region known to contain H3a. This contig refines the position of many genes and anonymous loci. In addition, 23 new sequence-tagged sites are described that further increase the genetic resolution surrounding H3a. A novel assay was developed to determine the location of H3a within the contig. Representative YACs were modified by retrofitting with a mammalian selectable marker, and then introduced by spheroplast fusion into mouse L cells. YAC-containing L cells were screened for the expression of the YAC-encoded H3a(a) Ag by using them as targets in a cell-mediated lympholysis assay with H3a(a)-specific CTLs. A single YAC carrying H3a was identified. Based on the location of this YAC within the contig, many candidate genes can be eliminated. The data position H3a between Tyro3 and Epb4.2, in close proximity to Capn3. These studies illustrate how genetic and genomic information can be exploited toward identifying genes encoding not only histocompatibility Ags, but also any autoantigen recognized by T cells. 相似文献
80.
JW Brufsky D Ross-Degnan D Calabrese X Gao SB Soumerai 《Canadian Metallurgical Quarterly》1998,36(3):321-332
Three receptor tyrosine kinases of the PDGF receptor family (RTKP) that clustered within 1000 Kb of the mouse chromosome 5 constitute an interesting unit that are expressed in three distinct cell lineages essential for constructing hematopoietic tissues. Namely, the c-kit gene that is expressed in hematopoietic stem cells is flanked by pdgfr alpha and flk genes expressed respectively in stromal cells and vascular endothelial cells. In this article, we review our results on their expression in the embryonic hematopoietic tissues. We found that co-expression of Flkl and c-Kit was frequently detected either in vascular endothelial cells or hematopoietic cells in the early hematopoietic tissues. On the other hand, the three RTKPs are expressed in different cell lineages in the fetal liver. On the basis of this finding, we propose two modes of embryonic hematopoiesis; hematogenic angiopoiesis and hematopoiesis. 相似文献